israel journal of the liver and related sciences

For ๏ฌrst choice treatment of bleeding oesophageal varices - the only therapy that IMPROVES SURVIVAL * References: 1. Bosch et al. Seminars in Liver Disease 2008;28;3-25 2. Bosch J et al. Journal of Hepatology; 48 (2008); s68-s92 3. Cardenas A. Clin Liver Dis 14 (2010) 251-262 4. Doctor's lea๏ฌ‚et June 2010 *Approved indication: Bleeding oesophageal varices and treatment of type I hepatorenal syndrome Ferring Pharmaceuticals Ltd. P.O.Box 3551, Caesarea Industrial Park 38900, Israel Tel.:+972-4-6309500 Fax: +972-4-6309511 www.ferring.com

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Page 1: israel journal of the liver and related sciences

For first choice treatment of bleeding oesophageal varices - the only therapy that IMPROVES SURVIVAL *

References: 1. Bosch et al. Seminars in Liver Disease 2008;28;3-25 2. Bosch J et al. Journal of Hepatology; 48 (2008); s68-s923. Cardenas A. Clin Liver Dis 14 (2010) 251-2624. Doctor's leaflet June 2010

*Approved indication: Bleeding oesophageal varices and treatment of type I hepatorenal syndrome

Ferring Pharmaceuticals Ltd. P.O.Box 3551, Caesarea Industrial Park 38900, IsraelTel.:+972-4-6309500 Fax: +972-4-6309511www.ferring.com

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Effective viral suppression1,2 + high genetic barrier1,2

Treatment for Chronic Hepatits B

Indication: Baraclude is indicated for the treatment of chronic HBV in adults with compensated liver disease and evidence of active viral replication and persistently elevated ALT levels. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions: dosage adjustment is recommended for patients with renal impairment, possible acute exacerbation of hepatitis, a higher rate of serious hepatic adverse events has been observed in patients with decompensated cirrhosis, occurrences of lactic acidosis (in the absence of hypoxaemia), sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues, patients should be advised that therapy with entecavir has not been proven to reduce the risk of transmission of HBV and therefore appropriate precautions should still be taken, this medicinal product contains lactose. There are no adequate data from the use of entecavir in pregnant women.

References: 1. Baraclude (entecavir) MOH approved physician prescribing leaet, June 2009 2. Tenney DJ et al. Hepatology (2009) Vol 49, 1-12

Biotis Ltd. 22 Hamelacha St. P.O.Box 11372, Rosh Haโ€™Ayin, 48091 Tel: 03-9002050 Fax: 03-9002029 www.biotis.co.ilBiotis is an exclusive representative of selected brands of BMS

Please refer to Baraclude approved Israeli Ministry of Health Physician Prescribing Information

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HLA MATCHING WITH LIVER TRANSPLANTATION OUTCOME SUGGEST Nk ROLE VIA HLA-CW* ALLOANTIGENS

Amal Bishara, Ola Haj-Yehya-Abu-Aita and Rifaat SafadiTissue Typing Unit and Liver Unit, Gastroenterology Institute, Hadassah Medical Center, Jerusalem

HLA compatibility in liver-transplantation (LTx) is controversial. We aimed to explore a โ€œfive-year follow-up retrospective studyโ€ the effect of HLA-C polymorphism and cross-match (CM) on LTx-outcome. 130 LTx-recipients with CM and HLA-C typing were divided to groups of (1) 84-recipients with available data for donor-recipient HLA-C genotyping for matching and for serologic cross-match. (2) 117-recipients with available data for HLA-C (C1,C2) genotype and HLA-Bw. (3) 130-recipients with available data for the HLA-Cw alloantigen profile. Analysis was done to study correlations with rejection episodes, complications and survival after transplantation. Results showed no effects in outcome after LTx for Donor/recipient HLA-C matching or recipient HLA-C genotype. Serological-CM was a significant predictor for survival but not rejection episodes. The NCM-recipients enjoyed better survival compared to PCM (P=0.049). HLA-C/NCM co-analysis didnโ€™t reveal an additive factor. Among HLA-Cw* alleles, recipients expressing HLA-Cw*06 experienced a significant increase in rejection episodes along the 3-months interval following transplantation (P=0.043). Furthermore, we reported significant protective effect for Cw*04 allele (P=0.008) with no effects of HLA-Cw* alleles on survival outcome. NK-cells from HLA-Cw*06 recipient showed increased count and activity as compared to HLA-Cw*04 recipients. They also showed increased in-vitro hepatocyte (Hep3B-cells) killing compared to other HLA-Cw* subtypes. HLA-C matching have no crucial effect on LTx-outcome, the serologic-CM predicts survival outcome but not rejection episodes. HLA-Cw*04 allele has a protective effect and HLA-Cw*06 allele has a risk effect for rejection episodes and NK are suggested to mediate this effect. This will help predict graft acceptance and planning effective immune-suppression.

TWO DECADES OF LIVER TRANSPLANTATION IN ISRAEL

M. Carmiel-HaggaiThe West Galilee Hospital and the Israeli National Transplantation Center

During 1991-2011 769 liver transplantation were performed and registered in the Israeli National Transplantation Center. The majority (82%) of liver transplantations were adult cadaveric donor. During the last 5 years the use of living donor liver transplantation had increase from 4% to 18.6% in adults. There was an increase of pediatric transplantation from 9%

(2% from living donors) to 16.5% while half were living donor. Simultaneous liverโ€“kidney transplantations (SLK) accounts for 4-5% of all transplantations, regardless of the change in the allocation scheme to MELD score during 2005. The most common primary liver disease among liver transplant patient is HCV (34%) although the leading cause for liver transplantation during the last 5 years is hepatocellular carcinoma (31%). Average one year patient and graft survival accounts for 79% and 78.3% respectively. Five years patients survival during 1991-1999 was 63% and 72% during 2000-2010, with annual mortality rate of 2.4% beyond the first year after transplant. Urgent re-transplantation was done on 7% of cases. The use of old donors had increased in the last decade: during 1991-1999 donors older than 50 were used in only 36.6% of cases while in the last 10 years they account for 48%. In conclusion: During two decades of liver transplantation in Israel, facing a severe shortage of organs there is an increase usage of living donation for pediatric and adults. The use of living donor for urgent adult liver transplantation is common.

HEPATIC 13 C-METHACETIN METABOLISM CORRELATES WELL WITH THE HEPATIC VENOUS PRESSURE GRADIENT (HVPG) IN PATIENTS WITH CIRRHOSIS

Reuben A1,2, Guggenheim G3, Hershkowitz A3, Ben Oren I3, Ilan Y2

1Medical University of South Carolina, Charleston SC, USA; 2Liver Unit, Hadassah Medical Center, Ein Kerem, Jerusalem, Israel; 3Exalenz Bioscience Limited, Modiโ€™in, Israel.

Background: In patients with cirrhosis, portal hypertension (PHTN) leads to life-threatening complications i.e. bleeding esophageal (EVs) and gastric varices, ascites, sepsis and renal failure. Blood tests and imaging may detect cirrhosis, but do not predict clinical outcomes. HVPG โ‰ฅ 10 mm Hg, (termed Clinically Significant Portal hypertension, CSPH), predicts many of the outcomes of cirrhosis and therapy of PHTN, but it is invasive and inconvenient for serial use. 13 C-Methacetin Breath Testing (MBT) assesses well the derangement of liver metabolism in cirrhosis, and therefore might correlate with the severity of PHTN. Aim: To compare results of MBT and HVPGs in patients with biopsy-proven cirrhosis. Methods: Results of MBT, HVPG, and clinical variables (demographics, causes and complications of cirrhosis, blood tests, and imaging) were recorded from 13 men and 8 women who underwent transjugular liver biopsy and hepatic venous pressure measurement. Correlation was sought between MBT results and HVPG. Results: Mean age was 58 years ยฑ 9.3 SD; all 21 subjects were Caucasian and had cirrhosis. Mean BMI was 33 ยฑ 6.4, and 33% were obese. Cirrhosis was caused by Nonalcoholic Steatohepatitis (7), Hepatitis C (6), Alcoholic Liver Disease (4), Primary Biliary Cirrhosis (2), Autoimmune Hepatitis (1) or was Cryptogenic (1).

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Of the 12 subjects with EVs (1 of whom had bled), 8 were treated with non-selective ฮฒ-blockers; 7 subjects had ascites treated with diuretics,but only 1 had encephalopathy. Mean Child-Turcotte-Pugh and MELD scores were 7ยฑ 2.2 and 10 ยฑ6.6, respectively. MBT correlated well with HVPG (r=0.75, AUC = 0.8 for CSPH), irrespective of varices, ascites or ฮฒ-blocker and/or diuretic use. Conclusions: MBT, which correlates well with HVPG in subjects with compensated or mildly decompensated cirrhosis and detects CSPH, may be a valuable noninvasive surrogate for assessment of PHTN and a useful aid in ฮฒ-blocker doseregulation.

SORTILIN, A NEW PLAYER IN HEPATIC STELLATE CELL ACTIVATION AND LIVER FIBROSIS

Einav Hubel, Isabel Zvibel, Zamir Halpern, Rafael BruckThe Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Background/Aims: Hepatic stellate cells (HSCs) were identified as the major collagen-producing cells in the injured liver. Following liver injury of any etiology, HSCs become activated, transitioning from quiescent cells into proliferative, fibrogenic and contractile myofibroblasts. The neurotrophin receptor p75NTR was shown to be crucial for HSC activation and development of liver fibrosis. In the present study, we investigated whether its co-receptor sortilin is also necessary for HSC activation. Methods: A bile duct ligation (BDL) model was used to evaluate fibrosis in wild type (WT) and sortilin-/- mice. The severity of the fibrosis was assessed by Sirius Red staining. Fibrogenic activity and pro-inflammatory cytokine expression were evaluated by qRT-PCR and Western blots. Primary HSC from WT and sortilin-/- mice were isolated, cultured for 14 days and treated with NGF and proNGF in order to determine apoptosis, proliferation, fibrogenic and pro-inflammatory cytokine genes.Results: Sirius Red staining in the BDL model showed significantly decreased fibrosis in sortilin-/- mice. In accordance with the Sirius Red results, expression of ฮฑ-smooth muscle actin, collagen I and TIMP-1 mRNA was significantly lower in sortilin-/- mice. Paradoxically, liver injury and inflammation, as determined by AST, ALT, TNFฮฑ and IL-6 mRNA, were higher in sortilin-/- mice. In vitro treatment revealed that proNGF induced SDF1, an activation marker, in HSC from WT, but not from sortilin -/- mice. Conclusions: Reduced fibrosis in sortilin -/- mice in a BDL model may be due either to reduced HSC activation or to increased HSC sensitivity to bile acidโ€“induced apoptosis.

SORTILIN, A NEW PLAYER IN HEPATIC STELLATE CELL ACTIVATION AND LIVER FIBROSIS

Einav Hubel, Isabel Zvibel, Zamir Halpern, Rafael BruckThe Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Background/Aims: Hepatic stellate cells (HSCs) were identified

as the major collagen-producing cells in the injured liver. Following liver injury of any etiology, HSCs become activated, transitioning from quiescent cells into proliferative, fibrogenic and contractile myofibroblasts. The neurotrophin receptor p75NTR was shown to be crucial for HSC activation and development of liver fibrosis. In the present study, we investigated whether its co-receptor sortilin is also necessary for HSC activation. Methods: A bile duct ligation (BDL) model was used to evaluate fibrosis in wild type (WT) and sortilin-/- mice. The severity of the fibrosis was assessed by Sirius Red staining. Fibrogenic activity and pro-inflammatory cytokine expression were evaluated by qRT-PCR and Western blots. Primary HSC from WT and sortilin-/- mice were isolated, cultured for 14 days and treated with NGF and proNGF in order to determine apoptosis, proliferation, fibrogenic and pro-inflammatory cytokine genes.Results: Sirius Red staining in the BDL model showed significantly decreased fibrosis in sortilin-/- mice. In accordance with the Sirius Red results, expression of ฮฑ-smooth muscle actin, collagen I and TIMP-1 mRNA was significantly lower in sortilin-/- mice. Paradoxically, liver injury and inflammation, as determined by AST, ALT, TNFฮฑ and IL-6 mRNA, were higher in sortilin-/- mice. In vitro treatment revealed that proNGF induced SDF1, an activation marker, in HSC from WT, but not from sortilin -/- mice. Conclusions: Reduced fibrosis in sortilin -/- mice in a BDL model may be due either to reduced HSC activation or to increased HSC sensitivity to bile acidโ€“induced apoptosis.

HBV INDUCES ITS OWN COACTIVATOR PGC-1A VIA CELLULAR OxIDATIVE STRESS

Iddo Bar-Yishay, Maya Mouler Rechtman, Zamir Halpern and Amir ShlomaiThe Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Hepatitis B Virus (HBV) is a prevalent hepatic infection and is a major cause of hepatic cirrhosis and the development of hepatocellular carcinoma (HCC). HBV is coactivated by Peroxisome Proliferator-Activated Receptor-ฮณ Coactivator 1a (PGC-1a), a central regulator of hepatic gluconeogenesis and energy homeostasis that is differentially expressed in response to metabolic cues. However, it is not clear whether and how the virus controls the expression of its own coactivator to enable its propagation. Here we show that PGC-1ฮฑ is robustly induced in the presence of HBV. PGC-1ฮฑ up-regulation is HBV dependant since Lamivudine treatment or alternatively HBV knockdown result in abrogation of PGC-1ฮฑ induction. Mechanistically, HBV expression results in a significant increase in Cytochrome C Oxidase activity, a central enzyme in the oxidative phosphorylation chain (OXPHOS), resulting in increased production of Reactive Oxygen Species (ROS), which are known inducers of PGC-1ฮฑ. Furthermore, treating HBV expressing cells with the anti-oxidant N-AcetylCysteine (NAC) results in abrogation of PGC-

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1ฮฑ induction. We conclude that HBV induces its own coactivator PGC-1ฮฑ, thus creating a positive feedback loop, possibly mediated by cellular oxidative stress.

THE ROLE OF THE UNFOLDED PROTEIN RESPONSE IN HEPATIC CARCINOGENESISScaiewicz V1, Nahmias A1, Barda L1, Parchack E1, B. Tirosh2, O.Shibolet3

1Liver Unit, Division of Medicine, Hadassah-Hebrew University Medical Center, 2Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Jerusalem, Israel .3Liver Unit, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel.

Background: The endoplasmic reticulum (ER) is responsible for protein folding and modification. ER stress occurs when the amount of protein entering into the ER exceeds its folding capacity, inducing a cyto-protective reaction collectively termed the unfolded protein response (UPR). Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. ER stress has been suggested to play a potential role in hepatic pathology and chronic inflammation. However, its role in HCC has not been addressed. Aim: We hypothesized that ER Stress is activated during hepatic carcinogenesis, and may play an important role in cancer initiation and/or progression. Methods: We used quantitative PCR analysis and western blotting on total RNA and protein respectively, isolated from liver tumors and parenchyma of DEN, a chemically induced, HCC mouse model. Immunohistochemistry staining for UPR proteins was performed on human tumor tissue collected from the Hadassah-Hebrew University Medical Center tissue bank. The research was approved by the institutional review board. Results: we observed a 3-fold increase in the spliced form of XBP1 mRNA and a 6-fold increase of CHOP mRNA in tumors, when compared to un-involved parenchyma. Downstream UPR target genes including ERDJ4 and p58ipk showed only a mild elevation, which may suggest a partial or aborted activation of the UPR. Immunohistochemistry staining results showed that XBP1 and CHOP were localized to the nucleus of cancerous cells. Sections from human lung, colon and hepatocellular carcinomas were also analyzed by Immunohistochemistry staining. Results showed that in all analyzed samples, CHOP was located in the nucleus of tumor cells, indicating activation. However, despite the known pro-apoptotic role of CHOP, we found no activation of apoptosis as assessed by activated caspase-3 staining. ATF6 was also localized to the nucleus of cancerous cells, while no nuclear staining was observed in un-involved parenchyma. Conclusions: We found that UPR is partially activated in tumor tissue from chemically induced HCC mouse model and human carcinomas, but not in un-involved parenchyma. The physiologic role of this activation is currently unclear. Activation of UPR proteins in HCC may mark this pathway as a possible target for therapeutic intervention.

NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) INDEPENDENTLY PREDICTS TYPE-2 DIABETES AND PRE-DIABETES DURING A SEVEN-YEAR PROSPECTIVE FOLLOW-UP

Shira Zelber-Sagi1,2, Roni Lotan*1,3, Oren Shibolet1,3, Muriel Webb1, Assaf Buch1,3, Zamir Halpern1,3, Erwin Santo1,3, Ran Oren1,3 1Dept. Gastroenterology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel2School of Public Health, Haifa University, Haifa, Israel3The Sackler Faculty of Medicine Tel-Aviv University, Israel*Equal contribution to the first author

Background and Aims: NAFLD is suspected to confer an increased risk for type-2 diabetes (DM), but only few prospective studies have been performed. The aim was to evaluate the independent role of NAFLD in predicting the development of pre-DM. Methods: a prospective cohort of a sub-sample of the Israeli National Health Survey evaluated at baseline and after 7-years by identical protocols. Metabolic parameters and ultrasonographic evidence of NAFLD were evaluated in 213 subjects, with no known liver disease or history of alcohol abuse. Exclusion criteria were DM or pre-DM at the baseline survey. The definition of pre-DM was: fasting glucose >100 mg/dl and/or A1C >5.7. Steatosis was quantified by ultrasound with the hepatorenal ultrasound index (HRI), representing the ratio between the mean brightness level of the liver and the right kidney. Results: The study included 141 volunteers (mean age 48.8ยฑ9.7, 50.4% male, 24.8% baseline NAFLD). Subjects with incident pre-DM had higher baseline prevalence rates of NAFLD as compared to controls (33.8% vs. 14.1%, P=0.007) and higher levels of baseline HRI (1.3ยฑ0.4 vs. 1.1ยฑ0.3, P=0.001). Baseline NAFLD (OR=3.6, 1.3-9.6 95%CI) or HRI (OR=4.7, 1.3-17.5 95%CI) were independent predictors for incident pre-DM in a multivariate logistic regression analysis adjusting for age, gender, BMI, abdominal obesity and a family history of type-2 DM. Furthermore, adjustment for physical activity, dietary intake of fat, carbohydrates, different types of fat and fiber did not weaken the association. Conclusion: NAFLD patients should be classified as a population at risk and closely monitored for the development of DM.

CHRONIC HBV INFECTION IN ISRAEL

Eli Zuckerman, Hedy S. Rennert, Shalev Zuckerman, Gad RennertLiver Unit and Department of Community Medicine and Epidemiology Carmel Medical Center and CHS National Cancer Center, Haifa, Israel

Epidemiological data of hepatitis B virus infection (HBV) in Israel is limited as large population-based studies have not performed so far. The aim of this study was to collect epidemiological, co-morbidities and natural history data of HBV infection in the largest population-based study ever performed in Israel.Methods: Data were obtained from the computerized records and database of Clalit Health Services (CHS) (established in the year 2000). The database contains information regarding

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demographic parameters, laboratory tests and pharmacy records, hospitalization and primary care physician records and death-related data.Results: Through 1.2002-10.2010, 870,124- out of 3,970,563 (21.9%) CHS ensured individuals were tested for HBV. 15,258 individuals (1.75%) were identified as positive for HBsAg (0.38% of CHS ensured individuals). HBV infection was more common in males (60% vs. 40%), in the Arab population (2.76% vs. 1.49 in non- Arabs) whereas the most prevalent age groups were 40-59 year-old. The prevalence of positive HBsAg among young individuals (age< 18) was 1.76% but only 5.2% were tested, while among adults > 20% were tested for HBsAg. We were able to map areas with high prevalence of HBV infection (โ‰ฅ5%), among these were many rural Arabic villages. The prevalence of HBsAg-positivity was different according to the country of origin: higher (3->5%) among subjects born in North Africa and in the republics of Central ( former USSR) and among refugees from Africa whereas among Israel-born individuals it was 1.3%. Of 282,596 individuals who were tested for HBcAb, 16.1% were positive for HBcAb-only. Data regarding HBsAb status, co-morbidities and natural history are still being analyzedConclusions: This is the first and the largest epidemiological study on HBV infection ever performed in Israel. Data regarding epidemiology, co-morbidities, treatment and natural history are provided and may help identifying high-risk populations .

HEPATITIS B SURFACE ANTIBODY DISAPPEARANCE IN PEDIATRIC LIVER TRANSPLANTED PATIENTS

Yael Mozer-Glassberg1, Raanan Shamir1,2, Eitan Mor2,3, Ran Steinberg2,4, Ari Silbermintz1, Rachel Bergerin1, Rivka Shapiro1,2

1Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, 2Sackler Faculty of Medicine, Tel-Aviv-University, Tel Aviv, 3Department of Transplantation, Rabin Medical Center, Petah-Tikva,4Organ Transplant Unit, Schneider Childrenโ€™s Medical Center of Israel, Petach Tikva, Israel.

Background: Hepatitis B virus (HBV) is one of the most common etiologies for liver disease worlwide. Chronic HBV frequently progress to cirrhosis and liver failure with or without hepato-cellular carcinoma. Universal vaccination against hepatitis B was implemented in Israel in 1992, with vaccination compliance of 95% of the population. Prior works showed that up to 10 % of vaccine recipients fail to respond with adequate anti-hepatitis B surface antibodies (anti-HBs) levels after a primary series of vaccinations. In addition, anti-HBs levels are expected to decline with time. This has important implications for populations under immunosuppressive treatment. AIMS: To determine HBV immunity in pediatric liver transplant patients and to observe HBsAb status under immunosuppressive therapy.Methods: A retrospective electronic chart review of pediatric liver transplanted patients, who were followed up at the liver-intestinal

transplantation unit at the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel (SCMCI) between 01/1995-12/2011. Charts were reviewed for HBV serology and immunization status. Immunization for HBV (HBsAb positivity) was defined by HBsAb titer > 10mIU/ml. Results: Overall, we retrieved 100 liver transplanted pediatric patientsโ€™ records. Prior to Transplantation data regarding HBV immunity was available for 41 patients (41%), all of them were negative for HBsAg or HBcAb. Out of these, only 28 patients (68.3%) were HBsAb positive. During follow up, eleven patients (39.3%) lost their protective antibodies. Median time for antibodies disappearance was 51 months (range: 15-114months). Only 8/28patients (28.5%) kept their immunity during the follow up period.Conclusions: Our data suggest that loss of HBV immunity during follow up of pediatric liver transplantation patients is common. Whether this loss of response differs from the general population needs to be determined. Regardless of the cause, major attempt should be made to asses HBV immunity status prior to transplantation and during follow up

THE EFFECT OF PARATHYROID HORMONE RELATED PEPTIDE (PTHRP) ON LIVER FIBROSIS

Shirley Abramovitch, Efrat Sharvit, Amir Ben Tov, Yosef Weisman, Shimon Reif Pediatric gastroenterology, Tel-Aviv Sourasky Medical Center

Background: Parathyroid hormone related peptide (PTHrP), is widely expressed in normal and malignant tissue. It may act as paracrine or autocrine factor. PTHrP shares the same N-terminal end as parathyroid hormone and therefore it can bind to the same receptor, the Type I PTH receptor (PTHR1). PTHrP was found to be involved in pro-inflammation process, cytokines release, induced expression and activation of fibrotic mediators and increase expression of fibrotic markers in lung and renal tissues. Yet, little is known about the effect of PTHrP on liver fibrosis.Aims: To examine whether PTHrP and its receptor are expressed in Hepatic stellate cells (HSCs), to investigate their effects on HSCs proliferation and to assess the effect of PTHrP on fibrotic markers. Methods: The experiments were performed on primary HSCs isolated from ratโ€™s livers. The presence of PTHrP and PTH receptor were examined by real-time PCR. The effect of PTHrP on HSCs proliferation was measured using BrdU kit and fibrotic markers were assessed by real-time PCR.Results: PTHrP and its receptor were found to be expressed on activated primary HSCs. HSCs treated with PDGF and TGF-ฮฒ1 up-regulated PTHrP mRNA expression by ~6 folds, and TGF-ฮฒ1 also up-regulated PTH-1 receptor mRNA expression by ~3.5 folds. PTHrP had no effect on HSCs proliferation, but it increased collagen Iฮฑ1 mRNA expression in a dose dependent manner.

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Conclusions: PTHrP showed profibrotic effect, therefore inhibition of PTHrP maybe a potential target for amelioration of liver fibrosis.

MICROCAPSULES MADE OF BIOSYNTHETIC HYDROGEL SCAFFOLDS FOR INTRAVASCULAR LIVER TISSUE REGENERATION THERAPY

O. Nayshool3, J. Carmel1, T. Saadi1, A. Arish2, Z. Bramnik2, I. Mironi-Harpaz4, D. Seliktar4, Y. Baruch1,3

1Liver Unit, 2Department of Surgery B, Rambam - Health Care Campus, 3Bruce Rappaport Faculty of Medicine, 4Department of Biomedical Engineering, Technoin- Israel Institute of Technogolgy, Haifa, Israel.

Introduction: The liver is the natural microenvironment for hepatocytes transplantation but unfortunately engraftment efficiency is low. We have developed hydrogel scaffolds that can be used for intra-hepatic or intravascular injection. They are made of fibrinogen crosslinked with polyethylene glycol (PEG-Fib) - diacrylates side chains, that form a hydrogel when mixed with cells and exposed to UV light. The hydrogel scaffolds may reduce shear stress and immediate immunological pressure after intravascular injection and thus may improve engraftment. Aims: Assessment of intraportal transplantation of PEG-Fib microcapsules with HuH7 cells and adult hepatocytes.Methods: Development of the model of intravascular transplantation of encapsulated cells. Assessment of encapsulated cell viability (PI/FDA). Comparing engraftment efficiency of encapsulated and non-encapsulated cells in rat model in-vivo using semiquantitative PCR (human 16q23.1) or real time qPCR (rat SRY-gene) and histology.Results: HuH-7 cell-polymer constructs were transplanted to the liver, spleen and sub cutis allowing cells to proliferate for two weeks. The viability of cells immediately after preparation of microcapsules was 70%. Microcapsules cell constructs at a size of 200-700 mm comprising HuH-7 or adult hepatocytes have been successfully injected into portal vein and transplanted cells were shown at 24h, 72h and 168h after procedure by histology and PCR. When adult hepatocytes viability was compared with and without the polymer we found early loss of cells but very good long term survival.Conclusions: The cells within the constructs after intraportal transplantation were viable for a week. This is an important method for the development of intravascular liver tissue engineering.

THE PRO-FIBROTIC EFFECTS OF PREGNANCY IN A HEPATIC FIBROSIS MICE MODEL

Johnny Amer, Rami Grifat, Lina Abu-Tair, Sarit Doron, Rufayda Mruwat, Carmel Kasher, Areej El-Khatib, Rifaat SafadiLiver Unit, Gastroenterology Institute, Hadassah Medical Center, Jerusalem

Background: Immune-cells interact with hepatic-stellate-cells (HSCs) in the development of liver fibrosis. Little is known about

the influence of pregnancy on development of hepatic-fibrosis. Aim: To explore the influence of pregnancy on progression of hepatic fibrosis. Methods: Four-groups of female-mice (C57Blc) were used (N=46). Pregnant were compared to non-pregnant groups in naive vs. fibrotic states. Hepatic-fibrosis was induced by 4-injections of peritoneal carbon-tetrachloride-(CCl4) within 10 days, starting at day 10 of documented-pregnancy. At end of experiment, serum samples were obtained for ALT determination. Harvested livers were evaluated for liver injury through histology, tissue protein and mRNA extracts (for western blot and RT-PCR analysis of aSMA expressions). Isolated intra-hepatic lymphocytes were assessed by flow-cytometry. Isolated lymphocytes and serum samples; collected form all groups; were in vitro co-cultured for 48 hours with primary isolated naรฏve HSCs. Washed cells were trypsinized, harvested, stained and analyzed by flow cytometry for phagocytosis (anti-ฮฑSMA+/anti-CD45+) and proliferations (CSFE). Results: CCl4-model for liver injury was well tolerated when induced in pregnancy similar to non-pregnant state. Hepatic-fibrosis (Masson-Trichrom-stain & ฮฑSMA- expressions) and necro-inflammation (H&E stain & serum-ALT levels) significantly increased in pregnancy. Increased liver-injury was accompanied with pro-fibrotic lymphocyte profile; CD8-subsets increased and NK-cells decreased. HSCs activation significantly increased when in-vitro cultured with lymphocytes from pregnant as compared to non-pregnant fibrotic donors. Pro-fibrotic profile was also explained by decreased NK-activity (CD107a marker) and of their phagocytosis. Moreover, serum samples from fibrotic-pregnant mice induced higher HSCs proliferations. Conclusions: Liver-fibrosis was severe in pregnant-model; via pro-fibrotic lymphocyte and serum alterations.

REMOVAL OF HEPATITIS C VIRUS-INFECTED CELLS BY A ZYMOGENIZED BACTERIAL TOxIN

Assaf Shapira1,2, Shiran Shapira3,4, Meital Gal-Tanamy2, Romy Zemel2, Itai Benhar1, Ran Tur-Kaspa2,5

1Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Israel 2Molecular Hepatology Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Petah Tikva, Israel 3The Integrated Cancer Prevention Center, Tel Aviv Medical Center, Tel-Aviv, Israel 4Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel 5Department of Medicine D and Liver Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.

Hepatitis C virus (HCV) treatment is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent HCV post liver transplantation. Here, we present a proof of concept for potential new anti-viral agents that will specifically eradicate virally infected cells, thus limiting virus production and spread. Our system is based on the E. coli chromosomal MazEF toxin-antitoxin system, which is composed of two active protein components: the long lived MazF toxin (ribonuclease) and the labile MazE antitoxin. We designed

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an HCV NS3 protease-activatable recombinant toxin which we named โ€œzymoxinsโ€ by constructing an expression cassette that encodes for a single polypeptide that incorporates both the toxin (MazF ribonuclease) and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. The MazF-based zymoxin, that is introduced to target cells by means of adenovirus mediated gene delivery, shows almost no toxicity to naive cells and high responsiveness to even low HCV protease level. It eradicates NS3-protease expressing cells and HCV (full virus) infected cells with remarkable efficiency and specificity. Moreover, treatment with MazF-based zymoxin showed a โ€œcuring effectโ€ upon partially infected culture, considerably eradicating the HCV infected cells while preserving the general population of cells, suggesting it as a potential new means of fighting HCV infection. Moreover, Zymoxins seem to be especially favorable for prevention and treatment of recurrent HCV post liver transplantation. Zymoxins represent a potential new means of fighting viral diseases and a valuable tool for eradication of cells infected by intracellular pathogens expressing intracellular proteases.

HCV TREATMENT RESULTS IN LIVER TRANSPLANT RECIPIENTS, SINGLE CENTER ExPERIENCE

Liat Mlynarsky1, Adam Phillips A1, Paulina Katz2, Menahem Ben-Chaim2, Michal Carmiel-Haggai3, Oren Shibolet1, Helena Katchman1

1Liver Unit, Department of Gastroenterology. 2Organ Transplantation Unit, Department of Surgery; Tel Aviv Sourasky Medical Center and The Sackler School of Medicine, Tel Aviv University, Tel-Aviv. 3The Western Galilee Hospital, Naharia

Background: Hepatitis C (HCV) is the most common indication for liver transplantation (OLT) in the western world and recurrence of HCV after transplantation is almost universal. Treatment of HCV following transplantation represents a special challenge. Methods: We conducted a retrospective case-control study of HCV transplanted patients in our center from1992-2010. Data included: HCV treatment before and after transplantation, complications and deaths. Results: Eighty-two HCV patients underwent transplantation. Twenty-two were excluded: second transplantation (2), liver- kidney transplantation (3), HIV co-infection (2), early post-transplantation death (within 3 months) (6). Nine patients were lost for follow up and were also excluded. 50/60 of the remaining patients had documented HCV recurrence. Anti-viral treatment was started in 35 patients. Five patients are still being treated or SVR results are still pending. Treatment was prematurely stopped in 10 patients (lack of response (2), adverse events (8). SVR was achieved in 33% (10/30 patients), while in patients that received a full course of treatment SVR rates reached 45% (9/20 patients). SVR markedly improved post-OLT survival (100% vs. 81% 5-years survival in patients with/without SVR respectively). Patients that failed therapy had short-term survival similar to untreated patients (81% vs. 80% 5-years survival respectively),

but some long-term survival benefit was observed (74% vs. 59% 10-years respectively). We observed higher SVR rates in naรฏve vs. treatment-experienced patients. Conclusion: SVR rates in HCV transplanted patients were 33%, comparable with world experience. SVR conferred a marked survival benefit. Predictors of SVR in transplanted patients should be further evaluated.

COMBINATION OF VITAMIN D WITH SITAGLIBTIN/METFORMIN IMPROVE LIVER FAT AND TRIGLYCERIDE CONTENT IN MICE WITH FATTY LIVER DISEASE

Vintfield Y, Krichevsky L, Svzalb S, Grosovski M,Bar Guy N and Assy NLiver Unit, Pathology department. Ziv Medical Center. Biotechnology, Ort Braude College. Faculty of Medicine, Bar-ilan university, Safed, Galilee, Israel

Background: Currently there is no established treatment for fatty liver disease. Vitamin D and Sitaglibtin/Metformin have shown anti inflammatory and anti oxidative effects. Aim: Evaluate the effects of Vitamin D with Sitaglibtin/Metformin on the hepatic fat, lipogenesis, inflammation, oxidation parameters in mice with NAFLD. Methods: A total of 33 mice were randomly divided into five groups. The mice in the control group were on chow diet (n = 10, gr 1), mice with NAFLD (n = 7, gr 2), mice with vitamin D (4000IU/kg, n=6, gr 3), mice with (Sitaglibtin/Metformin, 200 mg/Kg, n=5, gr 4), and mice with combination of vitamin D and Sitaglibtin/Metformin ((n = 5, gr 5).Liver sections were examined for fat content, lipogenesis, inflammation, and oxidation. Results: Liver fat decreased to 50% with Vitamin D, 18% with Sitaglibtin/Metformin, and to (9%) with combination group, as compared to controls (70%, P<0.001). The increase in hepatic TG levels (mg/gr liver) was blunted by 60% with vitamin D (2.5 ยฑ 1.7), 54% with Sitaglibtin/Metformin (2.04ยฑ 0.4, P < 0.001), and -2.5% with combination group (4.47ยฑ 1.4) as compared with the controls (4.36ยฑ 4.0, P < 0.001). Hepatic MDA (mmole/L) decreased by 17% with vitamin D (42.2 ยฑ 25), 33% with Sitaglibtin/Metformin (34.2ยฑ 8.8) and 41% with combination group (29.7ยฑ 4.3) as compared to controls (50.5 ยฑ 50.0, P<0.001). Hepatic MTP, and PPAR-a proteins were unregulated while paraoxonase and TNF-a decreased significantly in all treatment groups, mostly with combination group (P<0.001). Hepatic cholesterol remained unchanged. Conclusion: Combination of vitamin D and Sitaglibtin/Metformin improved hepatic steatosis

THE EFFECTS OF HEPATIC IRON OVERLOAD OR DEFICIENCY IN THIOACETAMIDE INDUCED ACUTE LIVER INjURY

Zvi Ackerman1, Orit Pappo2, Gabriela Link 3, Kravitz Maya1 and Maria Grozovski4

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1Departments of Medicine, Mount Scopus Campus and 2Pathology, Hadassah - Hebrew University Medical Center, 3Department of Human Nutrition and Metabolism, Hebrew University - Hadassah Medical School, Jerusalem, Israel and 4Biotechnology Department, Ort Braude College of Engineering, Karmiel, Israel

Background/Aim: Increase in hepatic iron concentration (HIC) may augment the severity and progression while reduction of HIC may attenuate a variety of chronic, non-hemochromatotic liver disorders. It is not known whether manipulations in the HIC may exacerbate or attenuate acute liver injury (ALI) from various toxins, like thioacetamide (TAA). Methods: Rats were randomly divided into 6 subgroups: 2 control with "normal" hepatic iron concentration (HIC), 2 that were subjected to parenterally iron overload (PIIO), 1 that was subjected to orally induced iron overload (OIIO), 1 that received repeated phlebotomies. Four groups (one group from each category) were also subjected to TAA toxicity. Results: TAA administration to control rats induced severe hepatic cell necrosis and apoptosis associated with a tremendous increase in serum aminotransaminases and depletion of hepatic glutathione and anti-oxidative parameters. OIIO and PIIO increased HIC by 370% and 2041% respectively. OIIO and PIIO induced hepatocellular (parenchymal) and reticuloendothelial iron overload respectively. Compared to the control group with "normal" HIC, TAA administration induced an exacerbated ALI in the OIIO rats but an ALI of a similar magnitude, in the PIIO rats.TAA administration to the phlebotomized rats caused an elevation in serum aminotransaminases that was of similar magnitude to the control group, but with less hepatic inflammatory infiltrate, higher hepatic glutathione content and a better hepatic anti-oxidative enzyme profile.Conclusions: Hepatocellular iron overload, but not reticuloendothelial iron overload exacerbates TAA induced ALI. Phlebotomy may improve the hepatic anti-oxidative milieu and thus may mildly attenuate TAA induced ALI.

LAPAROSCOPIC HEPATECTOMY - PUSHING THE BOUNDARIES OF LAPAROSCOPIC SURGERY

Ido Nachmany, Yaakov Goichman, Joseph M Klausner, Menahem Ben-HaimAffiliation - Department of Surgery; Tel Aviv Sourasky Medical Center and The Sackler School of Medicine, Tel Aviv University.

Background: laparoscopic surgery has rapidly become the preferable mode of operation for many common pathologies. However, hepatectomy is still rarely performed by this method because of its complexity, lack of surgeon training in both liver and minimally invasive surgery and concern of major bleeding. In recent years instrumental advances and improved surgical techniques have made laparoscopic hepatectomy possible in selected patients. Aim: to report our early experience with laparoscopic hepatectomy in a single tertiary transplant/HPB center. Methods: we retrospectively analyzed data on all patients that underwent laparoscopic hepatectomy in 2011. Data included

demographics, indications for surgery, surgical details and post-op follow-up. Results: Sixteen patients underwent laparoscopic liver resection. There were 12 female (75%) and 4 male (25%). Mean age was 49.3 (range 22-74). Indications were colorectal metastases in 6 patients, giant hemangioma in 4, HCC in 2, adenoma in one, giant cyst in 2 and FNH in one. Two patients had underlying cirrhosis. Mean length of surgery was 202 minutes (range 58-316), and the mean blood loss was 271 ml. In 1 case we converted to open resection, due to poor progress. One patient required blood transfusion during surgery (1 unit). Mean post-op length of hospital stay was 4.6 days (range 1-9). Two patients experienced post-op bleeding, and one required per-cutaneous drainage. There were no liver-related or systemic complications. All patients achieved R0 resection. Patients were followed for 6.8 months (range 1-11). We did not observe delayed complications in any of them. Conclusions: We report our first 15 laparoscopic hepatectomies for malignant and non-malignant indications. Outcome was excellent and we did not observe any long term complications. The data suggest that laparoscopic hepatectomy is safe and effective in selected patients.

THE ROLE OF ESSENTIAL FATTY ACIDS (EFA) AND R6 DESATURASE AND SCD-1 IN INTRAUTERINE AND EARLY DEVELOPMENTAL PROGRAMMING OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN ADULT RODENTS

Kenneth Hollander1, Catherine Tempel-Brami3, Alicia Leikin Frenkel1, Menahem Feinaru1, Fred M Konikoff1,2

1Research Laboratory for Gallstones and Liver Lipid Metabolism, Tel Aviv University, 2Institute of Gastroenterology and Hepatology, Meir Medical center, Kfar saba, Israel, and 3MRI unit, Tel Aviv University, Israel.

Background: Fetal nutrient supply, including fatty acids, can induce lasting consequences that may influence susceptibility to adult NAFLD.Objective: To evaluate dietary fatty acids quality in pregnancy and lactation on developmental origins of NAFLD in adult offspring.Procedure: During pregnancy and lactation, C57Bl6/J mice were fed isocaloric diets containing 6% fat: control (C, soybean), saturated (SFA, coconut), n-3 (flaxseed) or n-6 (safflower). Adult offspring were challenged with a high fat diet (HFD, 60% lard) to induce NAFLD. Results: All comparisons are vs C: HOMA index was 10% higher in SFA; n-3 and n-6 were 65% and 35% lower. Body fat in n-3 was 50% lower. Liver lipids in n-3 and n-6 were 20 % and 40% lower whereas SFA was 36% higher. In combined genders liver/body weight ratio was lower for n-3 in C diets but paradoxically lower for SFA in separate and combined genders following HFD. ฮ”6 and ฮ”9 desaturase activities in liver and epididymal fat increased for n-3 and decreased for SFA. Liver ฮ”6 desaturase mRNA

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expression for EFA decreased while SFA was increased 1.6-fold in C diet. Liver ฮ”9 desaturase mRNA expression was decreased in C for SFA but significantly elevated in HFD. In hepatocytes, 64% of phosphatidylcholine species were altered between C and HFD; mainly due to SFA. Conclusion: Maternal saturated fatty acids favor, whereas unsaturated prevent NAFLD in adult offspring. Silencing of ฮ”6 and ฮ”9 desaturase gene expression in C diets may suggest a role of epigenetic DNA methylation.

LOW VITAMIN D LEVELS IN NONALCOHOLIC FATTY LIVER DISEASE ASSOCIATE WITH INSULIN RESISTANCE AND LIVER INjURY PROGRESSION VIA IMMUNE Nk MECHANISM

Mahamid Mahmud1,2, Ibrahim Abdullah1, Rami Ghantous1 , Johnny Amer3, Sarit Doron3 and Rifaat Safadi1,3 1The Liver Unit, Holy Family Hospital, Nazareth. 2Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem. 3Liver Unit, Gastroenterology Institute, Hadassah Medical Center, Jerusalem

We identified predictive factors for Nonalcoholic-Fatty-Liver-Disease (NAFLD) outcome from liver biopsy reports 2000-2011 in Holy-Family-Hospital-Nazareth. We included histological NAFLD>18-years, without metabolic-syndrome or other liver etiologies. Age, gender, BMI, histology (%steatosis, necro-inflammatory activity, fibrosis-scoring), serum vitamin-D levels, ALT, AST, serum-fasting-insulin levels, HbA1c, HOMA-IR score, TG, HDL, LDL and CRP were evaluated. In-vitro, lymphocytes obtained from low/normal vitamin-D donors were analyzed for NK-activity (CD107a)/ phagocytosis with human-hepatic-stellate-cell-line (HSCs-LX2). Our results showed 72-cases fulfill inclusion/exclusion criteria, 44-males, mean age at biopsy 39.4ยฑ10.6y, BMI 29ยฑ2.8. None had cirrhosis as scores were โ‰คF3 and โ‰คA3. Normal serum-vitamin-D found in 15 (21%, 9 men), insufficient in 21 (29.1%, 14) and deficient levels in 36-cases (49.9%, 21). Lower serum-vitamin-D significantly correlated with decreased hepatic-fat-content but increased liver-injury (CRP, fibrosis-scoring & necro-inflammatory-activity), insulin-resistance (serum insulin levels, HbA1c & HOMA-IR score) and CRP. CRP-levels had a significant positive correlation with LDL, CRP, HBA1C, insulin and HOMA-score. BMI had a significant positive correlation with AST, insulin and steatosis. Compared to normal vitamin-D levels with mild liver injury (A1/F1), lymphocytes from low vitamin-D donors increased the in-vitro activation of HSCs. In additions, NK-cells from low vitamin-D donors showed low count while increased activity accompanied with decreased phagocytosis suggesting impairment in their killing effects. Low vitamin-D serum levels predict severe insulin-resistant and liver-injury but decreased hepatic-content. Immunological explanations are suggested as a mechanism via immune-mechanism of NK-impairment.

ORAL ADMINISTRATION OF DT56A ExERTS A HEPATOPROTECTIVE EFFECT AND ALLEVIATES INSULIN RESISTANCE AND FATTY LIVER DISEASE

Yehudit Shabat, Yoav Lichtenstein, Lydia Zolotarov, Ami Ben Ya'acov, Yaron Ilan

Background: Imbalance of the immune system which leads to chronic inflammation is associated with insulin resistance and development of fatty liver disease. DT56a is an enzymatic isolate of soybeans that is used for the treatment of menopausal symptoms and osteoporosis and was suggested to exert an immune modulatory effect Aim: To determine the immune-modulatory and the hepatoprotective effects of oral administration of DT56a in animal models of immune mediated liver injury. Methods: DT56a was orally administered to mice with immune-mediated (ConcavalinA) hepatitis, leptin deficiency or high-fat diet models of NASH. The effects of DT56a on liver damage, insulin resistance and the distribution of regulatory T cells were assessed. Results: Oral administration of DT56a suppressed the immune-mediated liver damage induced by Concanavalin A, as indicated by decreased serum ALT, AST, IFNฮณ and TNFa levels (p<0.03). To determine the potential role of DT56a in NASH we have studied its effect in two models. In ob/ob mice, treatment with DT56a led to a significant reduction in liver enzymes, serum cholesterol and triglycerides levels (p<0.05) and to improvement in glucose tolerance test (p<0.005). These effects were accompanied by a significant increase in regulatory T cells. HFD mice treated with DT56a displayed improved insulin resistance and glucose tolerance test. These effects were associated with a significant decrease in several subsets of T regulatory cells (p<0.007) and an increase of NKT cells (p<0.03). Conclusions: Oral administration of DT56a exerts a hepatoprotective effect and alleviation of insulin resistance and NASH via the alteration of the distribution of regulatory T cells.

EFFECTS OF ARAMCHOL ON LIVER FAT CONTENT AND METABOLIC PARAMETERS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD): RESULTS OF A PHASE-II RANDOMIZED CLINICAL TRIAL

R. Safadi, FM. Konikoff, T. Gilat and the Aramchol's Israeli Research Group*

Background and aims: Aramchol is a novel compound designed to reduce liver fat by inhibiting Stearoyl-CoA desaturase1 (SCD1). Our aim was to evaluate the safety, pharmacokinetics and effects of two doses of Aramchol (300 and 100 mg) versus placebo in patients with NAFLD.Methods: This double blind, randomized, placebo controlled, phase-II trial included patients with histologically proven NAFLD

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without cirrhosis based on a biopsy performed during the preceding 18 months. Changes in liver triglyceride concentration in patients treated with Aramchol or placebo for 3-months were assessed by Nuclear Magnetic Resonance Spectroscopy (NMRS). Secondarily, changes in metabolic and lipid parameters were evaluated Patients were followed for 120 days. Results: 58 patients (52 steatosis, 6 steatohepatitis) completed the study. A reduction of 12.6% in liver fat content was observed in the 300 mg Aramchol treated group (p=0.01, t-test), while a change of -3.0% and +3.5% was observed in the 100 mg and placebo groups, respectively (n.s). In the 300 mg Aramchol treated group, ALT, HOMA, insulin levels and body weight were reduced while serum adiponectin levels and endothelial function increased, No changes were observed in the 100 mg or placebo groups. No changes were observed in plasma cholesterol, triglyceride or HbA1c levels between the groups.Conclusions: Aramchol is safe and well tolerated and exhibits plasma pharmacokinetics that supports once daily dosing. The reduction of liver fat content obtained in the 300 mg Aramchol treated group and positive results on several metabolic parameters suggest a therapeutic potential that warrants further investigations.

*Aramchol's Israeli Research Group: Dr. Rifaat Safadi, Hadassah University Hospital Ein Kerem and Holy Family Hospital, Nazareth; Prof Fred M Konikoff, Meir MC.; Prof. Tuvia Gilat, GalMed Medical Research; Dr. Itzchak Angel, GalMed Medical Research; Dr. Ziva Rosenthal-Galili, GalMed Medical Research; Prof. Eli Zuckerman, The Lady Davis Carmel MC; Dr. Sif Abo Mouch, Hillel Yafe MC; Prof. Alexander Fich, Soroka University MC; Dr. Assaf Issachar, Belinson Rabin MC; Prof. Emanuel Sikuler, Soroka University MC; Dr. Nimr Assy, Ziv MC; Prof. Yakov Baruch, Rambam MC; Dr. Alice Hershkovitz, Meir MC; Dr. Yoav Lurie, The Tel Aviv Sourasky MC; Dr. Mahmud Mahamid, Holy Family Hospital, Nazareth, Prof. Moshe Graif, Tel Aviv Sourasky MC; Prof. Naftali Stern, Tel Aviv Sourasky MC; Dr. Annat Blank, The Tel Aviv Sourasky MC ; Dr. Dafna Ben Ba'ashat, Tel Aviv Sourasky MC; Dr. Shira Zelber-Sagi, Tel Aviv Sourasky MC; Prof. Ran Oren, Hadassah University Hospital Ein Kerem

REDUCED HEPATIC INjURY IN TOLL-LIkE RECEPTOR 4โ€“DEFICIENT MICE FOLLOWING D-GALACTOSAMINE/LIPOPOLYSACCHARIDE-INDUCED FULMINANT HEPATIC FAILURE

Ziv Ben Ari1,4, Orna Avlas4,5, Orit Pappo2, Veacheslav Zilbermints3, Yelena Cheporko4, Asher Shainberg5, Eran Sharon3, Franklin Grief3, Edith Hochhauser4

1Liver Institute, 2Department of Histopathology, 3Department of Surgery A, Beilinson Hospital-Rabin Medical Center, Petah Tiqwa, 4Liver and Cardiac Research Laboratory, Felsenstein Medical Research Center, Petah Tiqwa, Sackler School of Medicine, Tel Aviv University, Tel Aviv5Gonda (Goldschmied) Medical Diagnostic Research Center, The Mina & Everard Goodman Faculty of Life Sciences Bar-Ilan University, Ramat Gan, Israel.

Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), D-galactosamine (GalN)-induced FHF is a well established model of liver injury in mice. Toll-Like Receptor 4 (TLR4) has been identified as a receptor for LPS. The aim of this study was to investigate the role of TLR4 in FHF induced by D-GalN/ LPS administration in mice. Wild type (WT) and TLR4

deficient (TLR4ko) mice were studied in vivo in a fulminant model induced by GalN/LPS. Hepatic TLR4 expression, serum liver enzymes, hepatic and serum TNF-ฮฑ and interleukin-1b levels were determined. Apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor-kappaฮฒ (NF-ฮบฮฒ and phosphorylated c-Jun hepatic expression were studied using Western blot analysis. All WT mice died within 24 hours after administration of GalN/LPS while all TLR4ko mice survived. Serum liver enzymes, interleukin-1b, TNF-ฮฑ level, TLR4 mRNA expression, hepatic injury and hepatocyte apoptosis all significantly decreased in TLR4ko mice compared with WT mice. A significant decrease in hepatic c-Jun and IkB signaling pathway was noted in TLR4ko mice compared with WT mice. In conclusion, following induction of FHF, the inflammatory response and the liver injury in TLR4ko mice was significantly attenuated through decreased hepatic c-Jun and NFฮบB expression and thus decreased TNF-ฮฑ level. Down-regulation of TLR4 expression plays a pivotal role in GalN/ LPS induced FHF. These findings might have important implications for the use of the anti TLR4 protein signaling as a potential target for therapeutic intervention in FHF.

THE EFFECT OF RESISTANCE TRAINING ON NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) A RANDOMIZED CLINICAL TRIAL

Assaf Buchโ€ 1,2, Muriel Webb1, Hanny Yeshua1,4, Ofer kiss1, Nahum Vaisman1,2, Naomi Fliss1,2, Zamir Halpern1,2, Erwin Santo1,2, Ran Oren1,2, Oren Shibolet1,2, Shira Zelber-Sagi1,3

1Dept. Gastroenterology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel; 2The Sackler Faculty of Medicine Tel-Aviv University, Israel; 3School of Public Health, Haifa University, Haifa, Israel; 4Clalit Health Services

Background and aims: The recommended treatment of NAFLD includes weight reduction and physical activity (PA), but data on the effect of resistance training (RT) PA in NAFLD is scant. Aim: to evaluate the effect of 3 months supervised RT on clinical and metabolic parameters in patients with NAFLD. Methods: A randomized clinical trial. Inclusion criteria were ultrasonographic finding of fatty liver and exclusion of secondary liver disease. Patients were randomly allocated to either supervised RT, three times weekly, for 3 months, or a control arm consisting of home stretching. Hepatic ultrasound, biochemical blood tests, anthropometric measurements and body composition by DEXA were assessed. Steatosis was quantified by ultrasound utilizing the hepatorenal-ultrasound index (HRI). Results: Thirty six patients completed the study (age 25-62, mean BMI 31.3ยฑ4.4). The two arms did not differ in age, gender and baseline BMI (Pโ‰ฅ0.20 for all). Within the RT group we observed significant reductions in HRI score, serum ALT and ferritin levels. AST levels decreased significantly in both arms but two fold more in the RT arm. Total fat tissue and trunk fat tended to decrease, while lean body mass increased in the RT arm. Opposite trends were observed in the stretching arm (Table).

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Conclusions: RT may serve as a complement to treatment for NAFLD patients and an alternative for patients with low motivation for aerobic PA.

Table. Within group comparisons (mean difference from baseline ยฑSD)

Parameter (units)P-value RT arm Stretching arm

HRI (score) -0.31ยฑ0.410.01

-0.08ยฑ0.240.18

ALT (U/L) -6.6ยฑ9.00.01

-1.71ยฑ8.700.43

AST (U/L) -4.25ยฑ5.410.007

-2.35ยฑ3.670.02

GGT (U/L) -5.00ยฑ11.720.12

2.71ยฑ13.940.18

Ferritin (ng/ml) -21.7ยฑ29.950.02

-4.50ยฑ32.40.63

Total fat tissue % -0.94ยฑ1.830.08

0.69ยฑ0.870.02

Trunk fat % -0.78ยฑ2.280.22

0.85ยฑ1.10.02

Lean body mass % 0.90ยฑ1.780.08

-4.36ยฑ13.800.26

LOW CYP1A2 ENZYME ACTIVITY PROTECTS FROM HEPATIC IRON OVERLOAD IN PATIENTS WITH ฮฒ-THALASSEMIA

Itamar Nitzan1, Shoshana Revel-Vilk2, Ada Godfarb3, Yaron Ilan4, Nilla Hemed4, Eyal Shteyer1 1Pediatric Gastroenterology Unit, Department of Pediatrics,2Pediatric Pediatric Hematology-Oncology Department, 3Hematology Department, 4Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.

Background: CYP1A2 is a cytochrome enzyme with a pivotal role in hepatic drug metabolism. It was shown that CYP1A2-/- mice are protected from hepatic iron toxicity. The aim of this study was to assess the activity of CYP1A2, by Methacetin breath test, in relation to iron load in ฮฒ-thalassemia (TM) patients. Methacetin is metabolized by CYP1A2, and can be measured by 13C-methacetin breath test (MBT, BreathIDยฎ Exalenz Bioscience). Methods: MBT was performed in children and adults with TM. MBT parameters including PDR peak (percent dose recovered per hour), cumulative percentage of 13C recovery at 20 minutes (CPDR20) after ingestion of methacetin and time to peak PDR (TTP) were correlated with various clinical, blood and MRI measures. Results: Thirty patients were enrolled into the study. The median age was 30 years (range 1-60y) and 56% were female. Fourteen patients had plasma ferritin level < 1000 mcg/l. The PDR peak and CPDR20 were significantly lower in patients with ferritin levels < 1000 mcg/l compared to those with ferritin levels > 1000

mcg/l. During the study period, 21 patients had T2* MRI scans. Liver MRI was normal (T2* MRI > 6.3 milliseconds) in 8 patients, and was not associated with any clinical parameter. These patients had a markedly decreased activity of CYP1A2 (PDR < 20%/hour) compared to those with abnormal MRI, and all were from Jewish Kurdistan origin. Conclusions: Our study suggests that, similar to the murin model, low activity of CYP1A2 protects from hepatic iron accumulation in transfusion depended TM patients.

LIVER FIBROSIS AS MEASURED BY TRANSIENT ELASTOGRAPHY GRADUALLY DECREASES DURING ANTIVIRAL THERAPY IN PATIENTS WITH HEPATITIS C VIRUS (HCV)

Liane Rabinowich1, Stella Levit1, Shira Zelber-Sagi1, Helena Katchman1, Muriel Webb1, Adam Phillips1, Rafi Bruck1, Yoav Luria2, Oren Shibolet1

1Liver Unit, Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and the Sackler School of Medicine, Tel Aviv University; 2Liver Unit, Digestive Diseases Institute, Shaarei Zedek Medical Center, the Hebrew University in Jerusalem, Jerusalem Israel.

Background: Treatment of Chronic hepatitis C virus (HCV) is associated with a decrease in hepatic fibrosis as manifested by improved liver stiffness (LS) measured by transient elastography (FibroScan). Aim: to assess changes in LS in HCV patients during anti-viral treatment. Methods: Patients with HCV who were candidates for standard pegylated-IFN plus ribavirin therapy were enrolled. LS was measured by transient elastography at the time of enrollment and sequentially at 2, 4, 12, 24, 48 and 72 weeks. For each measurement, LS was calculated both as maximal LS (max-LS) and average LS values of three readings performed. Results: Twenty-three patients were enrolled. There was a significant decrease of LS at the end of follow-up compared with the initial pre-treatment value (-2.47kPa +/-4.11, p=0.009 for max-LS and -2.16kPa +/-3.49, p= 0.007 for average-LS). Patients with initial higher LS values (correlating with F2-4 fibrosis stage) demonstrated a greater decrease in LS values at the end of follow-up (-3.91kPa +/- 4.70, p=0.008 for max-LS and -3.9kPa +/- 4.05, p=0.006 for average-LS). The decrease in LS was gradual along the course of treatment. A significant decrease in LS was noted as early as 4 weeks for average LS value (-1.016kPa +/- 2.19, p= 0.04) and at 12 weeks for maximal LS value (-1.82kPa +/- 3.24, p=0.013). Conclusion: LS decreases gradually during IFN-based therapy in patients with chronic HCV with significant reduction noticed as early as after 4 weeks of treatment.

FIRST IN ISRAEL LAPAROSCOPIC ROBOTICALLY ASSISTED LEFT LIVER LOBECTOMY

Evgeny Solomonov, Evitar Nesher, Michael Gourevich, Sigal Aizner, Ezra Shaharabani and Eytan Mor.

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“ืชื™

ืฉื ืก ื”

ืงืฆื™ืจื™ ื”ื›ื ืช

Hepato-Pancreato-Biliary Surgery Unit, Beilinson Campus, Rabin Medcal Center. Petah Tiqwa, Israel; Department of Organ Transplantation, Rabin Medical Center. Petah Tiqwa, Israel

Background: Da Vinci Surgical System is shown to be superior to traditional laparoscopic technique in regards to better, 360-degree range of motion Endo-Wrist instrumentation, 3-dimentional images and stable camera view. Robotic surgery for liver resections has not yet been widely reported. The aim of this presentation is to report the first known case of hepatic resection with the use of Robotic surgical system in Israel.Methods: A 22-year-old woman with multiple episodes of cholangitis was referred for surgical treatment. Preoperative evaluation disclosed an Echinococcal Centrally located Cyst and its communication with left hepatic duct and proximal dilatation of the left lobe bile ducts. CT scan and MRCP had shown normal right and main bile ducts. Serological results were positive for an echinococcus. She underwent robotic assisted anatomical left liver lobectomy Results: Liver transsection was achieved with Harmonic Scalpel and bipolar forceps without inflow clamping. Blood loss was minimal and the patient did not receive blood transfusion. Operative time was 360 min. The patient underwent urgent ERCP tree days after the surgery: dilated CBD seen and impacted small stone was removed from the papilla. Good bile flow was achieved. Further postoperative period was uneventful and the patient was discharged on the 7th postoperative day.Conclusion: The laparoscopic approach using Da Vinci Robotic System may enable complex liver resection allowing precise manipulation during anatomical hepatic lobectomy. Our first case demonstrates impressive ability of robotic technique during laparoscopic approach in such challenging area as a liver surgery.

COUNSELING PATIENTS WITH BUDD-CHIARI SYNDROME REGARDING PREGNANCY: IS IT TIME FOR A PARADIGM CHANGE?

Meir Mizrahi1, Uriel Elchalal2, David Varon3, Lilach Roemi1, Tomer Adar4, Shaima Ziadat1, Daniel Shouval1, Oren Shibolet5 1Gastroenterology and liver disease institute. Division of Medicine 2High-risk pregnancy clinic, Department of obstetrics and Gynecology 3Coagulation unit, Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem 4Digestive Diseases Institute Shaare Zedek Medical center,Jerusalem 5. Liver Unit, Department of Gastroenterology and Liver Disease, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

Background: Appropriate pregnancy counseling in Buddโ€“Chiari syndrome (BCS) patients is a difficult task. Aim: To assess pregnancy counseling practices and outcome in BCS. Methods: A telephone questionnaire with all BCS female patients in our institute. Data included: demographics, number of pregnancies, maternal and fetal complications, discipline of managing physician & counseling regarding pregnancy. Results: 72 BCS patients were screened, 38 were women of

childbearing age (18-45 years old) and 36 agreed to participate. Mean age at diagnosis was 30 years. BCS etiologies included: factor V Leiden, protein C/S, or antithrombin III deficiencies, anti-phospholipid syndrome, and polycythemia-vera. Sixteen patients (45%) tried to conceive and 12 (33%) had 25 deliveries. There was no maternal or fetal mortality. Mean gestational week at delivery was 36. Mean birth weight was 2424 gr. Pregnancy-related complications were: preterm labor and delivery (20%), hospitalization for supervision (12%), premature contractions (6%), vaginal bleeding (6%). Complications related to the underlying disease were abdominal pain (6%), ascites exacerbation (5%), hepatic vein occlusion (4%) and variceal bleeding (3%). 24 patients were advised not to conceive, 4 opted to avoid pregnancy on their own accord and 8 did not receive any recommendation. 21/28 (75%), 2/4 (50%), and 1/4 (25%) patients followed by a hepatologist, hematologist and rheumatologist respectively were advised not to conceive, of those, 9 (38%) became pregnant and had 22 deliveries Conclusions: maternal and fetal outcomes in BCS were favorable. Hepatologists were more likely to recommend avoidance of pregnancy. Re-evaluation of pregnancy decisions and recommendations in BCS is required.

MTOR ACTIVATION PLAYS A CRITICAL ROLE IN REGULATING ACETAMINOPHEN INDUCED HEPATOTOxICITY

Dotan Uzi1, Viviana Schiewitz1, Boaz Tirosh1, Oren Shibolet2

1Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Jerusalem, Israel .2Liver Unit, Tel Aviv Sourasky Medical Center & Tel-Aviv University, Tel-Aviv, Israel.

Background: Drug induced liver injury (DILI) is a leading cause of liver injury, liver transplantation and indication for drug withdrawal. Acetaminophen (N-acetyl-p-aminophenol-APAP) overdose is the leading cause of DILI in the western world. APAP heaptotoxicity is mediated via oxidative and ER stress. Recently mTOR, a key regulator of cellular homeostasis was shown to be involved in APAP-induced hepatotoxicity. Aims: To characterize mTOR pathway activation and crosstalk with the ER stress/UPR signaling, and to mechanistically define its role in liver injury caused by APAP. Methods & expected results: We used an established mouse model for APAP-induced liver injury. Our preliminary results indicate inhibition of mTOR signaling in vitro, while in vivo APAP activates mTOR in a time dependant manner, as indicated by AKT phosphorylation, leading to ribosomal-S6 phosphorylation. TSC1 KO mice, in which of the mTOR pathway is constitutively active, showed increased liver damage compared to controls following APAP administration, while mice treated with rapamycin, an mTOR inhibitor, were protected. Rapamycin treatment led to ER stress attenuation, indicated by downregulation of UPR targets and limited CHOP nuclear localization.

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”ืžืจืฅ 2012ืชื™

ืฉื  ื”

ืกื›ื 

ื”ืจื™

ืฆื™ืง

ืช

Conclusions: Our studies provide evidence of a pathological role for the mTOR pathway and its crosstalk with ER stress/UPR signaling in APAP-induced liver injury. These findings mark the mTOR pathway as a possible target for therapeutic intervention in APAP induced hepatotoxicity.

THE INHIBITORY EFFECT OF LIGANDS OF NUCLEAR RECEPTORS ON HEPATIC STELLATE CELL ACTIVATION AND PROLIFERATION IS MEDIATED BY DOWNREGULATION OF CELL CYCLE PROTEINS

Efrat Sharvit1, Shimon Reif2, Shirley Abramovitch2, Zamir Halpern1 and Rafael Bruck1 1Institute of Gastroenterology, and 2Dept. of Pediatrics, Tel Aviv Sourasky Medical Center, and The Sackler School of Medicine, Tel-Aviv University, Tel Aviv

Background/aims: Peroxisome proliferator activator receptors (PPAR) ligands have been shown to inhibit development of liver fibrosis. The role of all trans retinoic acid (ATRA) and its metabolite 9-cis retinoic acid (9-cis) is less clear. We investigated the ability of the combination of ligands of peroxisome proliferator activator receptor ฮณ (PPARฮณ) and retinoic acid receptor (RAR) in inhibiting liver fibrosis and the effects of ATRA, 9-cis and PPARฮณ ligand 15-deoxy-ฮ”12,14-prostaglandinJ(2)[PJ(2)] on proliferation

of primary hepatic stellate cells, and on PPARฮณ, ฮฑSMA gene and protein expression in these cells. Methods: We assessed proliferation of primary hepatic stellate cells by BrdU and crystal violet. Cell cycle was determined by FACS analysis. Cyclin D1, P21, P27, mTOR, p70S6K, collagen Iฮฑ1, and ฮฑSMA proteins were determined by western blot analysis. Results: Proliferation of primary HSCs was inhibited by the combination of 9-Cis, ATRA and PJ and the effect of the 3 ligands was additive. As demonstrated by FACS analysis, the inhibition of proliferation was due to cell cycle arrest. Studies using western blot analysis demonstrated reduced expression of cyclin D1 and increased expression of P21 and P27 by the above combination. When examining proteins leading to HSCs proliferation, we found that the 3 ligands down regulated the phosphorylation of mTOR and p70S6K. The combined treatment led to inhibition of relies of the lipid droplets as demonstrated by Oil red-O staining. Studies using real time PCR and western blot analysis showed marked inhibition of collagen Iฮฑ1 and ฮฑSMA in the presence of the combination of the 3 ligands.Summary: Our studies demonstrate that the combination of these 3 ligands inhibited the mTOR pathway which leads to inhibition of HSCs proliferation, G0/G1 arrest and affect cell cycle proteins. Furthermore, the combined treatment had antifibrotic effect.

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ื”ื˜ื™ืคื•ืœ ื”ื™ื• ื™ืขื™ืœื•ืช ื™ื•ืชืจ ื‘ืžื™ื“ื” ืžืฉืžืขื•ืชื™ืช ืกื˜ื˜ื™ืกื˜ื™ืช ืœืขื•ืžืช ืงื‘ื•ืฆืช ื”ื‘ื™ืงื•ืจืช. ืœื ื”ื™ื” ื”ื‘ื“ืœ ื‘ื™ืŸ ื”ืงื‘ื•ืฆื•ืช ืžื‘ื—ื™ื ืช ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™, ื•ืœื .HIV ืื• ื‘ืขื•ืžืก ื”ื ื’ื™ืคื™ ืฉืœ CD4 ื”ื™ื” ื”ื‘ื“ืœ ื‘ืจืžื•ืช ื”ืœื™ืžืคื•ืฆื™ื˜ื™ื ืžืกื•ื’ื”ืžื—ื‘ืจื™ื ืžืกื›ืžื™ื ืฉืฉืชื™ ืฉื™ื˜ื•ืช ื”ื—ื™ืกื•ืŸ ื”ื™ื• ื™ืขื™ืœื•ืช ื™ื•ืชืจ ืžื”ืคืจื•ื˜ื•ืงื•ืœ

.HIV ื”ืžืงื•ื‘ืœ ืœื—ื™ืกื•ืŸ ื—ื•ืœื™ืื™ ืืคืฉืจ ืœื“ื•ืŸ ื‘ื—ื™ืกื•ื ื™ื ืœโ€“HBV ื‘ืœื™ ืœื™ื™ื—ื“ ื›ืžื” ืžื™ืœื™ื ืœื‘ื˜ื™ื—ื•ืช ื”ื—ื™ืกื•ืŸ. ืœื—ื™ืกื•ื ื™ื ื ื’ื“ HBV ื™ืฉ ืคืจื•ืคื™ืœ ื‘ื˜ื™ื—ื•ืชื™ ืžืฆื•ื™ืŸ, ื•ืœืจื•ื‘ ืžืชืŸ ื”ื—ื™ืกื•ืŸ ืื™ื ื• ื›ืจื•ืš ื‘ืชื•ืคืขื•ืช ืœื•ื•ืื™ ืžืฉืžืขื•ืชื™ื•ืช. ื”ืชื•ืคืขื•ืช ื”ืฉื›ื™ื—ื•ืช ื”ืŸ ืชื’ื•ื‘ื” ื‘ืžืงื•ื ื”ื”ื–ืจืงื” ื›ื’ื•ืŸ ืจื’ื™ืฉื•ืช )17%-22%( ืื• ืื•ื“ื ื•ื ืคื™ื—ื•ืช )1%-10%(. ืชื•ืคืขื•ืช ืœื•ื•ืื™ ื›ืœืœื™ื•ืช ื™ื›ื•ืœื•ืช ืœื”ื™ื•ืช ืขื™ื™ืคื•ืช )13%-15%(, ื—ื•ื, ื›ืื‘ื™ ืจืืฉ, ื”ื–ืขื•ืช, ื‘ื—ื™ืœื•ืช ื•ื”ืงืื•ืช )<1%(. ืœืขืชื™ื ื ื“ื™ืจื•ืช ื“ื•ื•ื— ืขืœ ืชื•ืคืขื•ืช ืœื•ื•ืื™ ื›ื’ื•ืŸ ืชื’ื•ื‘ื” ืื ืืคื™ืœืงื˜ื™ืช, ืชื•ืคืขื•ืช ื ื•ื™ืจื•ืœื•ื’ื™ื•ืช ืื• ืคืจื™ื—ื•ืช ืกื™ืกื˜ืžื™ื•ืช )Steven Johnson syndrome(. ืœืคื ื™ ื›ืขืฉื•ืจ ื”ื•ืคื™ืขื• ื›ืžื” ื“ื™ื•ื•ื—ื™ื ืฉืงืฉืจื• ื‘ื™ืŸ ื”ื—ื™ืกื•ืŸ ืœโ€“HBV ืœื”ืฉืจื™ื” ืื• ืœื”ื—ืžืจื” ืฉืœ ื˜ืจืฉืช ื ืคื•ืฆื”. ื•ืขื“ืช ื‘ื“ื™ืงื” ืฉืœ ืืจื’ื•ืŸ ื”ื‘ืจื™ืื•ืช ื”ืขื•ืœืžื™ ืขื‘ืจื” ืขืœ ื”ืžื™ื“ืข ื•ืงื‘ืขื” ื›ื™ ืœื ื”ื•ื›ื— ืงืฉืจ ื‘ื™ืŸ ื”ื—ื™ืกื•ืŸ ืœื‘ื™ืŸ ื˜ืจืฉืช ื ืคื•ืฆื”, ืืš ื”ื•ืกื™ืคื” ื”ืขืจืช ืื–ื”ืจื” ื•ืœืคื™ื” ืœื’ื‘ื™ ื—ื•ืœื™ ื˜ืจืฉืช ื ืคื•ืฆื” ื™ืฉ ืœืฉืงื•ืœ ืืช ื”ืชื•ืขืœืช ื‘ื—ื™ืกื•ืŸ ืืœ ืžื•ืœ ื”ืกื›ื ื” ืœื”ื—ืžืจื” ื‘ืžื—ืœื”. ื›ืžื• ื›ืŸ ื‘ื›ืžื” ืžืงืจื™ื ืชื•ืืจ ืงืฉืจ ื‘ื™ืŸ ื”ื—ื™ืกื•ืŸ ืœื”ืชืคืชื—ื•ืช ืžื—ืœื•ืช ืื•ื˜ื•ืื™ืžื•ื ื™ื•ืช, ืœื•ื™ืงืžื™ื” ื•ืžื—ืœื•ืช ืื—ืจื•ืช, ืืš ื•ืขื“ื•ืช ื‘ื“ื™ืงื” ืฉืœ ืืจื’ื•ืŸ ื”ื‘ืจื™ืื•ืช ืœื ืžืฆืื• ืงืฉืจ ื›ื–ื”. ื”ื—ื™ืกื•ืŸ ื ื—ืฉื‘ ืœื‘ื˜ื•ื— ืขื‘ื•ืจ ื ืฉื™ื

ื”ืจื•ืช ื•ืžื ื™ืงื•ืช, ืืฃ ืฉืœื ื ื™ืชืŸ ื‘ืžืกื’ืจืช ืžื—ืงืจื™ืช.

ืกื™ื›ื•ืื”ื’ื•ืจื ืžืจื›ื–ื™, ืชื—ืœื•ืื” ื’ื•ืจื ื”ื•ื B ืžืกื•ื’ ื”ื›ื‘ื“ ื“ืœืงืช ื ื’ื™ืฃ ื•ืกืจื˜ืŸ ื”ื›ื‘ื“. ื•ื›ืจื•ื ื™ืช, ืฉื—ืžืช ืœื”ืชืคืชื—ื•ืช ืžื—ืœืช ื›ื‘ื“ ื—ืจื™ืคื”

ื—ื™ืกื•ืŸ ืขืœโ€“ื™ื“ื™ ืžื•ื—ืœื˜ืช ื‘ืฆื•ืจื” ื‘ืžื—ืœื” ื”ื™ื“ื‘ืงื•ืช ืœืžื ื•ืข ืืคืฉืจ ืื•ื ื™ื‘ืจืกืืœื™. ื›ื‘ืจ ื”ื™ื•ื ืื ื• ืจื•ืื™ื ื™ืจื™ื“ื” ื ื™ื›ืจืช ื‘ื”ื™ื“ื‘ืงื•ืช ื‘ืงืจื‘ ื•ื™ืจื™ื“ื” ืžืงื‘ื™ืœื” ื‘ืกื™ื‘ื•ื›ื™ ืžื—ืœื•ืช ื”ื›ื‘ื“ ื™ืœื“ื™ื ื‘ืืจืฆื•ืช ืื ื“ืžื™ื•ืช ื•ื‘ืขื™ืงืจ ืกืจื˜ืŸ ื”ื›ื‘ื“. ื”ืžืฆืืช ื”ื—ื™ืกื•ืŸ ื ื•ืœื“ื” ืžืชื•ืš ื”ื‘ื ืช ืžื‘ื ื” ื”ื ื’ื™ืฃ ื•ืžืขืจื›ืช ื”ื—ื™ืกื•ืŸ ื•ืฉื™ืœื‘ื” ืฉื™ื˜ื•ืช ืžื•ืœืงื•ืœืืจื™ื•ืช ืฉื”ืœื›ื• ื•ื”ืชืคืชื—ื• ืขื ื”ืฉื ื™ื. ื’ื ื™ืขื™ืœื•ืช ื”ื—ื™ืกื•ื ื™ื ื•ื‘ื˜ื™ื—ื•ืชื ื”ืฉืชืคืจื” ืขื ื”ื–ืžืŸ, ื•ื—ืœ ืžืขื‘ืจ ืžื—ื™ืกื•ื ื™ื ืฉืžืงื•ืจื ื‘ืกืจื•ื ืœื—ื™ืกื•ื ื™ื ืฉื™ื•ืฆืจื• ื‘ืฉื™ื˜ื•ืช ืจืงื•ืžื‘ื™ื ื ื˜ื™ื•ืช ื‘ืฉืžืจื™ื ื•ื‘ืชืื™ ื™ื•ื ืงื™ื. ืขื™ืงืจ ื”ืžืืžืฅ ื›ื™ื•ื ืžืชืžืงื“ ื•ื‘ื—ื™ืกื•ืŸ ืฉืœ ืื•ื›ืœื•ืกื™ื•ืช ื ื•ืกืคื•ืช ื‘ื”ื›ื ืกืช ืชื›ื ื™ื•ืช ื—ื™ืกื•ืŸ ืœืืจืฆื•ืช ืžื™ื•ื—ื“ื•ืช, ื•ื‘ื™ื ื™ื”ืŸ ื›ืืœื” ืฉืœื ื”ื’ื™ื‘ื• ืœื—ื™ืกื•ืŸ ืจื’ื™ืœ. ืžืืžืฅ ืขื•ืœืžื™ ื™ื‘ื˜ื™ื— ืžื ื™ืขื” ืฉืœ ืื™ืจื•ืขื™ ื”ื“ื‘ืงื” ื—ื“ืฉื™ื ื•ืื•ืœื™ ืืฃ ื”ื›ื—ื“ืช ื”ื ื’ื™ืฃ ืฉืœื™ื•ื•ื” ืืช

ื”ืื ื•ืฉื•ืช ืžืฉื—ืจ ื™ืœื“ื•ืชื”.

ื‘ื™ื‘ืœื™ื•ื’ืจืคื™ื”1. McMahon BJ, Bulkow LR, Singleton RJ, et al. Elimination of

hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program. Hepatology 2011;54:801-7.

2. Younossi ZM, Stepanova M. Changes in hepatitis A and B vaccination rates in adult patients with chronic liver diseases and diabetes in the U.S. population. Hepatology 2011;54:1167-78.

3. Launay O, van der Vliet D, Rosenberg AR, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA 2011;305:1432-40.

ืฉื›ื™ื—ื•ืช ื”ื”ื™ืืจืขื•ืช ืฉืœ ื–ื™ื”ื•ื ื—ืจื™ืฃ ื‘ึพHBV ืฆื ื—ื” ืžึพ19/100,000 ื‘ืงืจื‘ ื™ืœื™ื“ื™ ืืœืกืงื” ืžืชื—ืช ืœื’ื™ืœ 20 ื‘ืฉื ื™ื 1981โ€“1982, ืœึพ0/100,000 ื‘ืฉื ื™ื 1993โ€“1994 ื•ืœื ืชื•ืขื“ ืฉื•ื ืžืงืจื” ืฉืœ ื–ื™ื”ื•ื ื—ืจื™ืฃ ื‘ึพHBV ื‘ืงืจื‘ ื™ืœื“ื™ื

ืžืื– 1992.ื•ืขื“ืช ื‘ื“ื™ืงื” ืฉืœ ืืจื’ื•ืŸ ื”ื‘ืจื™ืื•ืช ื”ืขื•ืœืžื™ ืงื‘ืขื” ื›ื™ ืœื ื”ื•ื›ื— ืงืฉืจ ื‘ื™ืŸ ื”ื—ื™ืกื•ืŸ ืœื‘ื™ืŸ ื˜ืจืฉืช ื ืคื•ืฆื”, ืืš ื”ื•ืกื™ืคื” ื”ืขืจืช ืื–ื”ืจื” ื•ืœืคื™ื” ื‘ืงืจื‘

ื—ื•ืœื™ ื˜ืจืฉืช ื ืคื•ืฆื” ื™ืฉ ืœืฉืงื•ืœ ืืช ื”ืชื•ืขืœืช ื‘ื—ื™ืกื•ืŸ ืืœ ืžื•ืœ ื”ืกื›ื ื” ืœื”ื—ืžืจื” ื‘ืžื—ืœื”.

ืžื—ืœื•ืช ืœื”ืชืคืชื—ื•ืช ื”ื—ื™ืกื•ืŸ ื‘ื™ืŸ ืงืฉืจ ืชื•ืืจ ืžืงืจื™ื ื‘ื›ืžื” ืื•ื˜ื•ืื™ืžื•ื ื™ื•ืช, ืœื•ื™ืงืžื™ื” ื•ืžื—ืœื•ืช ืื—ืจื•ืช, ืืš ื•ืขื“ื•ืช ื‘ื“ื™ืงื” ืฉืœ ืืจื’ื•ืŸ ื”ื‘ืจื™ืื•ืช ืœื ืžืฆืื• ืงืฉืจ ื›ื–ื”. ื”ื—ื™ืกื•ืŸ ื ื—ืฉื‘ ืœื‘ื˜ื•ื— ืขื‘ื•ืจ ื ืฉื™ื ื”ืจื•ืช

ื•ืžื ื™ืงื•ืช, ืืฃ ืฉืœื ื ื™ืชืŸ ื‘ืžืกื’ืจืช ืžื—ืงืจื™ืช.

B ื—ื™ืกื•ื ื™ื ืœื ื’ื™ืฃ ื“ืœืงืช ื”ื›ื‘ื“ ืžืกื•ื’

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ืžืจืฅ 2012

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”

ืืช ื‘ ืฉืžื•ื›ื™ื—ื™ื ืžื—ืงืจื™ื ื›ืžื” ืคื•ืจืกืžื• ื”ืื—ืจื•ื ื” ืฉื ื” ื—ืฉื™ื‘ื•ืช ื”ื—ื™ืกื•ืŸ ืœื ื’ื™ืฃ ื“ืœืงืช ื”ื›ื‘ื“ ืžืกื•ื’ B ืื• ืฉืžืกืคืงื™ื ืชืฉื•ื‘ื” ืœืฉืืœื•ืช ื—ืฉื•ื‘ื•ืช ื‘ื ื•ื’ืข ืœื™ืขื™ืœื•ืช ื”ื—ื™ืกื•ืŸ ื‘ืื•ื›ืœื•ืกื™ื•ืช ืžื™ื•ื—ื“ื•ืช. ืžืชื•ืฆืื•ืช ื”ืžื—ืงืจื™ื ืขื•ืœื” ื›ื™ ื ื™ืชืŸ ืœืžื ื•ืข ืชื—ืœื•ืื” ื•ืœื”ื’ื™ืข

ืœืžื™ื’ื•ืจ ืฉืœ ืื—ืช ืžืžื—ืœื•ืช ื”ื›ื‘ื“ ื”ืงืฉื•ืช ื”ืงื™ื™ืžื•ืช ื›ื™ื•ื. ื”ืชื—ืœื•ืื” ืžื’ื•ืจืžื™ ืื—ื“ ื”ื•ื )HBV(ื B ืžืกื•ื’ ื›ื‘ื“ ื“ืœืงืช ื ื’ื™ืฃ ื”ื ืคื•ืฆื™ื ื‘ืขื•ืœื. ื›โ€“400 ืžืœื™ื•ืŸ ืื ืฉื™ื ื‘ืจื—ื‘ื™ ื”ืขื•ืœื ื”ื ื ืฉืื™ื ื›ืจื•ื ื™ื™ื ืฉืœ ื”ื ื’ื™ืฃ ื•ื—ืฉื•ืคื™ื ืœืกื›ื ืช ื”ืชืคืชื—ื•ืช ืฉืœ ืžื—ืœืช ื›ื‘ื“ ืกื•ืขืจืช, ืฉืœ ืฉื—ืžืช ื•ืฉืœ ืกืจื˜ืŸ ื›ื‘ื“. ืžื“ื™ ืฉื ื” ื ืจืฉืžื™ื ื›โ€“600,000 ืžืงืจื™ ืžื•ื•ืช

ื›ืชื•ืฆืื” ืžืกื™ื‘ื•ื›ื™ ืžื—ืœืช ื›ื‘ื“ ืฉื ื’ืจืžื” ื‘ืฉืœ ื”ื ื’ื™ืฃ ื•โ€“5 ืžื™ืœื™ื•ืŸ ื—ืจื™ืฃ ื–ื™ื”ื•ื ื™ืคืชื—ื• ืื“ื ื‘ื ื™ ืงื•ื“ืจื™ื ื ืชื•ื ื™ื ืœื ื•ื›ื— ื‘ื ื’ื™ืฃ. ืฉืžื“ื•ื‘ืจ ืœื–ื›ื•ืจ ื—ืฉื•ื‘ ืืœื”, ื‘ืžื—ืœื” ื ื™ืชื ืช ืœืžื ื™ืขื”. ื—ื™ืกื•ืŸ ื‘ืฉื™ืžื•ืฉ ื ืžืฆื ืœื ื’ื™ืฃ ื™ืขื™ืœ ื•ืชื›ื ื™ื•ืช ืฉื ื™ื ืžโ€“25 ืœืžืขืœื” ืงื™ื™ืžื•ืช ืื•ื ื™ื‘ืจืกืืœื™ื•ืช ื—ื™ืกื•ืŸ ื‘ืžืืžืจ ืžื“ื™ื ื•ืช. 180 ื‘ื›โ€“ืฉืœ ืžืงืžื”ื•ืŸ ื•ื—ื‘ืจื™ื• ืฉืคื•ืจืกื ื”ื—ื‘ืจื” ืŸ ื‘ื™ืจื—ื• 2011 ื‘โ€“ื”ื›ื‘ื“ ืœื—ืงืจ ื”ืืžืจื™ืงืื™ืช

ืžืชื•ืืจืช ื”ืฉืคืขืช ื”ื—ื™ืกื•ืŸ ืขืœ ืื•ื›ืœื•ืกื™ื™ื” ืฉืœ ื™ืœื™ื“ื™ื ื‘ืืœืกืงื” ื‘ืžืฉืš ืฉื›ื™ื—ื•ืช ื‘ืขื‘ืจ ื ืจืืชื” ื–ื• ื‘ืื•ื›ืœื•ืกื™ื™ื” .]1[ ืฉื ื” 25 ืฉืœ ืžืขืงื‘ ื’ื‘ื•ื”ื” ื‘ื™ื•ืชืจ ืฉืœ ื–ื™ื”ื•ื ื—ืจื™ืฃ ื•ื›ืจื•ื ื™ ื‘โ€“HBV ื•ืฉืœ ืกืจื˜ืŸ ื›ื‘ื“ ืจืืฉื•ื ื™ )Hepatocellular carcinoma(. ื‘ืฉื ื™ื 1982-1981 ื”ื—ืœื” ื‘ืืœืกืงื” ืชื›ื ื™ืช ืžืžืฉืœืชื™ืช ืœื–ื™ื”ื•ื™ ื›ืœ ื”ืžืงืจื™ื ืฉืœ ื–ื™ื”ื•ื ื—ืจื™ืฃ ื‘โ€“HBV ื•ืฉืœ ื›ืœ ืžืงืจื™ ืกืจื˜ืŸ ื”ื›ื‘ื“ ื”ืจืืฉื•ื ื™ ื‘ืงืจื‘ ื ืฉืื™ื ื›ืจื•ื ื™ื™ื, ื‘ืืžืฆืขื•ืช ื“ื™ื•ื•ื— ื•ืžื“ื™ื“ื” ืฉื ืชื™ืช ืฉืœ ื”ื—ืœื‘ื•ืŸ ื”ืขื•ื‘ืจื™ )Alpha-feto protein(. ื‘โ€“1984 ื”ื™ื™ืœื•ื“ื™ื, ืœื›ืœ ืื•ื ื™ื‘ืจืกืืœื™ืช ื—ื™ืกื•ืŸ ืชื›ื ื™ืช ืœื™ื™ืฉื ื‘ืืœืกืงื” ื”ื—ืœื• ื•ืชื›ื ื™ืช ืกืงืจ ื•ื—ื™ืกื•ืŸ ืœื›ืœ ื”ื™ืœื“ื™ื ื ืขืจื›ื” ื‘ื’ื ื™ ื”ื™ืœื“ื™ื ื•ื‘ื‘ืชื™ ื”ืกืคืจ. ื ื•ืกืฃ ืœื›ืš ื ืขืฉื” ื ื™ืกื™ื•ืŸ ืœืขื•ื“ื“ ื’ื ืžื‘ื•ื’ืจื™ื ืœื”ืชื—ืกืŸ ื‘ืืžืฆืขื•ืช ื”ื•ื“ืขื•ืช HBVโ€“ื‘ ื—ืจื™ืฃ ื–ื™ื”ื•ื ืฉืœ ื”ื”ื™ืืจืขื•ืช ืฉื›ื™ื—ื•ืช ื”ืจืคื•ืื™ื™ื. ื‘ืชื™ืงื™ื ืฆื ื—ื” ืžโ€“19/100,000 ื‘ืงืจื‘ ื™ืœื™ื“ื™ ืืœืกืงื” ืžืชื—ืช ืœื’ื™ืœ 20 ื‘ืฉื ื™ื 1982-1981, ืœโ€“0/100,000 ื‘ืฉื ื™ื 1994-1993, ื•ืœื ืชื•ืขื“ ืฉื•ื ืžืงืจื” ืฉืœ ื–ื™ื”ื•ื ื—ืจื™ืฃ ื‘โ€“HBV ื‘ืงืจื‘ ื™ืœื“ื™ื ืžืื– ืฉื ืช 1992. ื‘ืžืงื‘ื™ืœ, ื”ื™ืืจืขื•ืช ืกืจื˜ืŸ ื›ื‘ื“ ืจืืฉื•ื ื™ ื‘ืงืจื‘ ื™ืœื™ื“ื™ ืืœืกืงื” ืžืชื—ืช ืœื’ื™ืœ 20 ืฆื ื—ื” ืžโ€“3/100,000 ื‘ืฉื ื™ื 1984-1983 ืœโ€“0 ื‘ืฉื ื™ื 1999-1995, ื•ืœื ืชื•ืืจ ืืฃ ืžืงืจื” ืฉืœ ืกืจื˜ืŸ ื–ื” ื‘ืงืจื‘ ื™ืœื“ื™ื ืžืื– ืฉื ืช 1999. ืžืกืคืจื HBV ืฆืขื™ืจื™ื ืžื’ื™ืœ 20 )ื ืงื‘ืข ืขืœ ืคื™ ื‘ื“ื™ืงื” ืฉืœ ื ืฉืื™ื ื›ืจื•ื ื™ื™ื ืฉืœ ื—ื™ื•ื‘ื™ืช ืœโ€“HBsAg( ืฆื ื— ืžโ€“657 ื‘ืฉื ืช 1987 ืœโ€“2 ื‘ืฉื ืช 2008. ื”ื—ื•ืงืจื™ื ืžืกื›ืžื™ื ื•ืื•ืžืจื™ื ืฉื—ื™ืกื•ืŸ ืื•ื ื™ื‘ืจืกืืœื™ ืœื™ื™ืœื•ื“ื™ื ื•ืชื›ื ื™ืช ืกืงืจ ื•ื—ื™ืกื•ืŸ

ืœื™ืœื“ื™ื ื‘ืงืจื‘ ื™ืœื™ื“ื™ ืืœืกืงื” ื”ืขืœื™ืžื” ืœื—ืœื•ื˜ื™ืŸ ืืช ืžืงืจื™ ืกืจื˜ืŸ ื”ื›ื‘ื“ ื”ืจืืฉื•ื ื™ ื•ืืช ืžืงืจื™ ื”ื–ื™ื”ื•ื ื”ื—ืจื™ืฃ ื‘โ€“HBV ื‘ืงืจื‘ ื™ืœื“ื™ื. ื–ื•ื”ื™ ื”ื’ื™ืฉื”

ื”ื™ืขื™ืœื” ื‘ื™ื•ืชืจ ืœืžื ื™ืขืช ืชื—ืœื•ืื” ื”ืงืฉื•ืจื” ืœโ€“HBV ื‘ืงืจื‘ ื™ืœื“ื™ื. ืœื™ื™ืฉื•ื ืงืฉื•ืจื” HBVโ€“ืœ ื‘ื—ื™ืกื•ื ื™ื ื”ืขื™ืงืจื™ื•ืช ืžื”ื‘ืขื™ื•ืช ืื—ืช ื™ืจื•ื“ื” ืœื—ื™ืกื•ืŸ ื”ื”ืžืœืฆื•ืช ืœื—ื™ืกื•ืŸ ืžื‘ื•ื’ืจื™ื ื‘ืงื‘ื•ืฆื•ืช ืกื™ื›ื•ืŸ ื•ืœืชื’ื•ื‘ื” ื‘ืงื‘ื•ืฆื•ืช ืžื™ื•ื—ื“ื•ืช. ื‘โ€“2011 ืคื•ืจืกืžื• ืฉื ื™ ืžื—ืงืจื™ื ื—ืฉื•ื‘ื™ื ื‘ื ื•ืฉื ื–ื”. HBVโ€“ื ื‘ื“ืงื” ืžื“ื™ื ื™ื•ืช ื”ื—ื™ืกื•ืŸ ืœ Hepatologyโ€“ื‘ืขื‘ื•ื“ื” ืฉืคื•ืจืกืžื” ื‘ื•โ€“HAV ื‘ืงืจื‘ ื—ื•ืœื™ื ื‘ืžื—ืœืช ื›ื‘ื“ ื›ืจื•ื ื™ืช ื•ื—ื•ืœื™ ืกื•ื›ืจืช ]2[. ื™ืฉ ื”ืžืœืฆื” ืœื—ื™ืกื•ืŸ ืฉืœ ืฉืชื™ ื”ืงื‘ื•ืฆื•ืช ื”ืœืœื•, ืืš ืžื™ื“ืช ื”ื™ื™ืฉื•ื ืฉืœ ื”ื”ืžืœืฆื” ืื™ื ื” ื™ื“ื•ืขื”. ื”ืžื—ื‘ืจื™ื ืกืงืจื• ืื•ื›ืœื•ืกื™ื™ื” ืžืชื•ืš ืกืงืจ ื”ื‘ืจื™ืื•ืช ื”ืืžืจื™ืงืื™ National Health and Nutrition Examination Survey -( ื”ืขื ืง ื‘ืฉื ื™ื ื‘ืกืงืจ ืฉื ื›ืœืœื• ืื ืฉื™ื ื›โ€“25,000 ืกืงืจื• ื”ื .)NHANES

2008-1999. 14% ื•โ€“8.6% ืžื”ืžืฉืชืชืคื™ื ืกื‘ืœื• ืžืžื—ืœื•ืช ื›ื‘ื“ ื›ืจื•ื ื™ื•ืช ืื• ืžืกื•ื›ืจืช, ื‘ื”ืชืืžื”. ื”ื—ื•ืงืจื™ื ืžืฆืื• ืฉืฉื™ืขื•ืจ ื”ื—ื™ืกื•ืŸ ืœโ€“HAV ืขืœื” ื‘ืฉื ื•ืช ื”ืกืงืจ ืžโ€“13% ืœโ€“20% ื•ื‘ืงืจื‘ ื—ื•ืœื™ื ื‘ืžื—ืœืช ื›ื‘ื“ ื›ืจื•ื ื™ืช ืขืœื• ืฉื™ืขื•ืจื™ ื”ื—ื™ืกื•ืŸ ืžโ€“23% ืœโ€“32%. ื”ื—ื™ืกื•ืŸ ืœโ€“HAV ื ื™ืชืŸ ื‘ืขื™ืงืจ ืœื—ื•ืœื™ื ื‘ืžื—ืœืช ื”ื›ื‘ื“ ื”ืฉื•ืžื ื™, ื•ืื™ืœื• ื”ื—ื™ืกื•ืŸ ืœโ€“HBV ื ื™ืชืŸ ื’ื ืœื—ื•ืœื™ื ื‘ืžื—ืœืช

.C ื”ื›ื‘ื“ ื”ืฉื•ืžื ื™ ื•ื’ื ืœื ืฉืื™ื ื›ืจื•ื ื™ื™ื ืฉืœ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืžืกื•ื’ HAVโ€“ื‘ืงืจื‘ ื—ื•ืœื™ ื”ืกื•ื›ืจืช ื ืจืืชื” ืขืœื™ื™ื” ืฉืœ ื›โ€“7% ื‘ืฉื™ืขื•ืจื™ ื”ื—ื™ืกื•ืŸ ืœ

ื•โ€“HBV ื‘ืžื”ืœืš ืฉื ื•ืช ื”ืกืงืจ, ื‘ื“ื•ืžื” ืœืื•ื›ืœื•ืกื™ื™ื” ื”ื›ืœืœื™ืช. ืฉื™ืขื•ืจื™ ื”ื—ื™ืกื•ืŸ ืœโ€“HAV ื•ืœโ€“HBV ื”ื ืื—ื“ ืžืžื“ื“ื™ ื”ืื™ื›ื•ืช ื‘ืžืขืจื›ืช ื”ื‘ืจื™ืื•ืช ื‘ืืจื”"ื‘. ื‘ื‘ื“ื™ืงื” ืœืžื“ื“ื™ ืื™ื›ื•ืช ืืœื” ื ืชื’ืœื” ืฉืฉื™ืขื•ืจ ื”ื—ื™ืกื•ืŸ ืœโ€“HAV ื™ืจื“ ื‘ืื•ื›ืœื•ืกื™ื™ื”, ืืš ืฉื™ืขื•ืจ ื”ื—ื™ืกื•ืŸ ืœโ€“HBV ืขืœื” ืžโ€“31% ืœโ€“41%. HBVโ€“ื•ืœ HAVโ€“ื”ื›ื•ืชื‘ื™ื ืžืกื›ืžื™ื ื•ืื•ืžืจื™ื ื›ื™ ืืžื ื ืฉื™ืขื•ืจื™ ื”ื—ื™ืกื•ืŸ ืœื‘ืงืจื‘ ื—ื•ืœื™ื ื‘ืžื—ืœืช ื›ื‘ื“ ื›ืจื•ื ื™ืช ืื• ืกื•ื›ืจืช ืขื•ืœื™ื, ืืš ื”ื ืขื“ื™ื™ืŸ ื ืžื•ื›ื™ื HBVโ€“ื•ื‘ HAVโ€“ืžืื•ื“. ืœื ื•ื›ื— ื”ืžืฉืžืขื•ืช ื”ืงืœื™ื ื™ืช ื”ื’ื“ื•ืœื” ืฉืœ ื–ื™ื”ื•ื ื‘ืืฆืœ ื—ื•ืœื™ ืžื—ืœืช ื›ื‘ื“ ื›ืจื•ื ื™ืช ื•ื—ื•ืœื™ ืกื•ื›ืจืช ื™ืฉ ืžืงื•ื ืœื™ื™ืฉื•ื ืžื•ื’ื‘ืจ ืฉืœ

ื”ื”ืžืœืฆื•ืช ืœื—ื™ืกื•ืŸ ื‘ืื•ื›ืœื•ืกื™ื•ืช ืืœื•.ื‘ืขื‘ื•ื“ื” ืฉื ื™ื™ื” ืฉืคื•ืจืกืžื” ื‘ื™ืจื—ื•ืŸ ืฉืœ ื”ื—ื‘ืจื” ื”ืืžืจื™ืงืื™ืช ืœืจืคื•ืื” )JAMA( ื ื‘ื“ืงื” ืฆื•ืจืช ื”ื—ื™ืกื•ืŸ ื”ื™ืขื™ืœื” ื‘ื™ื•ืชืจ ื‘ืื—ืช ืžืงื‘ื•ืฆื•ืช ื”ื—ื•ืœื™ื ื”ืงืฉื•ืช ื‘ื™ื•ืชืจ ืœื—ื™ืกื•ืŸ, ื—ื•ืœื™ HIVื ]3[. ื‘ืขื‘ื•ื“ื” ื ื‘ื“ืงื• 3 ืฉื™ื˜ื•ืช ืœื—ื™ืกื•ืŸ: ืืจื‘ืข ื–ืจื™ืงื•ืช ืชื•ืšโ€“ืฉืจื™ืจื™ื•ืช ืฉืœ ืžื™ื ื•ืŸ ื›ืคื•ืœ ืฉืœ ื—ื™ืกื•ืŸ ืจืงื•ืžื‘ื™ื ื ื˜ื™ )20 ืžื™ืงืจื•ื’ืจื ื‘ืฉื‘ื•ืขื•ืช 0, 4, 8 ื•โ€“24(, 4 ื–ืจื™ืงื•ืช ืชื•ืšโ€“ืขื•ืจื™ื•ืช ืฉืœ ืžื™ื ื•ืŸ ื ืžื•ืš )4 ืžื™ืงืจื•ื’ืจื( ื‘ืื•ืชื ื–ืžื ื™ื ื•ืคืจื•ื˜ื•ืงื•ืœ ื”ื—ื™ืกื•ืŸ ื”ืจื’ื™ืœ ืฉืœ 3 ื–ืจื™ืงื•ืช ืชื•ืšโ€“ืฉืจื™ืจื™ื•ืช )20 ืžื™ืงืจื•ื’ืจื ื‘ืฉื‘ื•ืขื•ืช 0, 4 ื•โ€“24(. ื‘ืฉื‘ื•ืข ื”โ€“28 ื ื‘ื“ืงื” ื”ืชื’ื•ื‘ื” ืฉืœ ื—ื•ืœื™ื ืฉืงื™ื‘ืœื• ืœืคื—ื•ืช ื–ืจื™ืงืช ื—ื™ืกื•ืŸ ืื—ืช. ื‘ื™ืŸโ€“ ื™ื—ื™ื“ื•ืช 10 ืœโ€“HBs ื‘ืจืžื” ืฉืœ ื ื•ื’ื“ื ื™ื ื›ืจืžืช ื”ื•ื’ื“ืจื” ืชื’ื•ื‘ื”

ืœืื•ืžื™ื•ืช/ืž"ืœ ืœืคื—ื•ืช. ืชื’ื•ื‘ื” ื—ื™ื•ื‘ื™ืช ื ืžืฆืื” ืืฆืœ 82% )95% ืจื•ื•ื— ืกืžืš 77%-88%( ืžื”ืžื—ื•ืกื ื™ื ื‘ืงื‘ื•ืฆืช ื”ืžื™ื ื•ืŸ ื”ื›ืคื•ืœ ืฉืœ ื”ื–ืจืงื” ืชื•ืšโ€“ืฉืจื™ืจื™ืช, ืืฆืœ 77% )95% ืจื•ื•ื— ืกืžืš 69%-84%( ื‘ืงื‘ื•ืฆืช ื”ื”ื–ืจืงื” ื”ืชื•ืšโ€“ืขื•ืจื™ืช, ื•ืจืง ืืฆืœ 65% ื‘ืงื‘ื•ืฆื” ื”ื—ื™ืกื•ืŸ ื”ืจื’ื™ืœ )95% ืจื•ื•ื— ืกืžืš 56%-72%(. ืฉืชื™ ืงื‘ื•ืฆื•ืช

ื—ื™ืกื•ื ื™ื ืœื ื’ื™ืฃ ื“ืœืงืช ื”ื›ื‘ื“ ืžืกื•ื’ B - ืขื“ื›ื•ืŸ ืื•ืจืŸ ืฉื‘ื•ืœืชืื“ื ืคื™ืœื™ืคืก

ื™ื—ื™ื“ืช ื”ื›ื‘ื“, ื”ืžื›ื•ืŸ ืœืžื—ืœื•ืช ื“ืจื›ื™ ื”ืขื™ื›ื•ืœ ื•ื”ื›ื‘ื“, ื”ืžืจื›ื– ื”ืจืคื•ืื™ ืช"ื ืข"ืฉ ืกื•ืจืืกืงื™ ื•ืื•ื ื™ื‘ืจืกื™ื˜ืช ืช"ื

ืฉื›ื™ื—ื•ืช ื”ื”ื™ืืจืขื•ืช HBVืฉืœ ื–ื™ื”ื•ื ื—ืจื™ืฃ ื‘ึพืฆื ื—ื” ืžึพ19/100,000 ื‘ืงืจื‘ ื™ืœื™ื“ื™ ืืœืกืงื” ืžืชื—ืช ืœื’ื™ืœ 20 ื‘ืฉื ื™ื 1982-1981 - 100,000/0, ื‘ืฉื ื™ื 1994-1993, ื•ืœื ืชื•ืขื“ ืฉื•ื ืžืงืจื” ืฉืœ ื–ื™ื”ื•ื ื—ืจื™ืฃ ื‘ึพHBV ื‘ืงืจื‘ ื™ืœื“ื™ื ืžืื– ืฉื ืช 1992

ื‘ื“ื”ื›

ืช ืง

ื“ืœ ืœ

ืื ื™

ืกื•ื—ื™

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸื ื‘ื“ืงื• 4 ืžื—ืงืจื™ื ืฉื‘ื”ื ื”ืฉืชืžืฉื• ื‘ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ ืœื˜ื™ืคื•ืœ ื‘ื—ื•ืœื™ ื›ื‘ื“ ืฉื•ืžื ื™, ื‘ื—ืœืงื ื ื™ืชื ื” ืชื•ืกืคืช ืฉืœ ื•ื™ื˜ืžื™ืŸ E ื•ื‘ื—ืœืงื ืœื ื ื™ืชื ื” ืชื•ืกืคืช ื›ื–ื•. ื‘ื›ืœ ื”ืžื—ืงืจื™ื ื ืขืฉื• ื‘ื™ื•ืคืกื™ื•ืช ื›ื‘ื“. ื‘ืžื—ืงืจ ืฉืคื•ืจืกื ื‘โ€“2010 ื‘โ€“NEJM ื•ื›ืœืœ 247 ืžื˜ื•ืคืœื™ื ืขื ื›ื‘ื“ ืฉื•ืžื ื™ ืœืœื ืกื•ื›ืจืช, 80 ืžื˜ื•ืคืœื™ื E ืงื™ื‘ืœื• ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ ื‘ืžื™ื ื•ืŸ ืฉืœ 80 ืž"ื’ ืœื™ื•ื, 84 ืžื˜ื•ืคืœื™ื ืงื™ื‘ืœื• ื•ื™ื˜ืžื™ืŸื‘ืžื™ื ื•ืŸ ืฉืœ 800 ืž"ื’ ืœื™ื•ื ื•โ€“83 ืžื˜ื•ืคืœื™ื ืงื™ื‘ืœื• ืคืœืฆื‘ื• ืœืชืงื•ืคื” ืฉืœ 96 ืฉื‘ื•ืขื•ืช. ืืฆืœ ืžื˜ื•ืคืœื™ื ืฉืงื™ื‘ืœื• ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ ื ืจืืชื” ื™ืจื™ื“ื” ื‘ืจืžื•ืช ืื ื–ื™ืžื™ ื”ื›ื‘ื“ ื•ื‘ืจืžืช ื”ืฉื•ืžืŸ ื‘ื›ื‘ื“ ื•ื—ืœ ืฉื™ืคื•ืจ ื‘ื—ืœืง ืžื”ืžืจื›ื™ื‘ื™ื ื”ื“ืœืงืชื™ื™ื )LOBULAR INFLAMMATION & BALLONING DEGENERATION( ืœืœื ืฉื™ืคื•ืจ ืžืฉืžืขื•ืชื™ ื‘ืจืžืช ื”ืคื™ื‘ืจื•ื–ื™ืก ื”ื›ื‘ื“ื™. ืืฆืœ ื”ืงื‘ื•ืฆื” ืฉืงื™ื‘ืœื” ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ ืœื ื ืจืื” ื™ืชืจื•ืŸ ืžื‘ื—ื™ื ืช ื”ืฉื™ืคื•ืจ ื‘ืจืžื” ื”ื”ื™ืกื˜ื•ืœื•ื’ื™ืช ื™ื—ืกื™ืช

ืœืงื‘ื•ืฆื” ืฉืงื™ื‘ืœื” ื•ื™ื˜ืžื™ืŸ E. ื‘โ€“3 ืžื—ืงืจื™ื ื ื•ืกืคื™ื ืฉื›ืœืœื• ื‘ืกืš ื”ื›ื•ืœ 149 ื—ื•ืœื™ื, ื ืžืฆื ืฉื™ืคื•ืจ ื‘ืจื•ื‘ ื”ืžื“ื“ื™ื ื”ื”ื™ืกื˜ื•ืœื•ื’ื™ื™ื ื‘ืขืช ืžืชืŸ ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ

ืœื—ื•ืœื™ื ื”ืกื•ื‘ืœื™ื ืžื›ื‘ื“ ืฉื•ืžื ื™.

ืžื’ื‘ืœื•ืช ื”ืžื—ืงืจื™ื ืจื•ื‘ ื”ืžื—ืงืจื™ื ื›ืœืœื• ืžืกืคืจ ืงื˜ืŸ ืฉืœ ื ื‘ื“ืงื™ื, ื”ื˜ื™ืคื•ืœ ื ื™ืชืŸ ืœืชืงื•ืคื” ืงืฆืจื”, ื•ืœื ื‘ื›ื•ืœื ื ืขืฉื• ื‘ื™ื•ืคืกื™ื•ืช ื›ื‘ื“. ื‘ื—ืœืง ืžื”ืขื‘ื•ื“ื•ืช ื”ืœื™ื›ื™ ื”ืžื—ืงืจ

ืœื ื‘ืจื•ืจื™ื, ื•ื”ืื™ื›ื•ืช ื”ืžืชื•ื“ื•ืœื•ื’ื™ืช ืฉืœ ื—ืœืงื ืœืงื•ื™ื”.

ืกื™ื›ื•ื ื›ื™ื•ื•ืŸ ืฉืจื•ื‘ ื”ืžื—ืงืจื™ื ืฉื‘ื—ื ื• ืขื“ ื”ื™ื•ื ืืช ื”ืฉื™ืžื•ืฉ ื‘ืžื˜ืคื•ืจืžื™ืŸ ืœื˜ื™ืคื•ืœ ื‘ืžื—ืœืช ื”ื›ื‘ื“ ื”ืฉื•ืžื ื™ ืฉืœื ืขืœ ืจืงืข ืืœื›ื•ื”ื•ืœ ื”ืชื‘ืกืกื• ืขืœ ืงื‘ื•ืฆื•ืช ื›ื•ืœื ื”ื›ื™ืœื• ืงื‘ื•ืฆืช ื•ืœื ื–ืžืŸ ืงืฆืจ ื ืžืฉื›ื• ืงื˜ื ื•ืช ืฉืœ ืžืฉืชืชืคื™ื, ืื™ืŸ ื”ืžืœืฆื” ืœื”ืฉืชืžืฉ ืœื”ื™ื•ื ื ื›ื•ืŸ ื”ื™ืกื˜ื•ืœื•ื’ื™ืช, ื•ื”ืฉื•ื•ืื” ื‘ื™ืงื•ืจืช ื‘ืื•ืคืŸ ืฉื’ืจืชื™ ื‘ืžื˜ืคื•ืจืžื™ืŸ ื‘ืงืจื‘ ืžื˜ื•ืคืœื™ื ื”ืกื•ื‘ืœื™ื ืžื›ื‘ื“ ืฉื•ืžื ื™

ืœืœื ืกื•ื›ืจืช.ื›ืš ื’ื ืœื’ื‘ื™ ื”ืฉื™ืžื•ืฉ ื‘ื˜ื™ืื–ื•ืœื™ื“ื™ื ื“ื™ื•ื ื™ื - ืจื•ื‘ ื”ืžื—ืงืจื™ื ื ืขืฉื• ืขืœ ืงื‘ื•ืฆื•ืช ืงื˜ื ื•ืช, ื—ืœืงืŸ ื”ื˜ืจื•ื’ื ื™ื•ืช, ื•ื—ืœืงื ื ืžืฉื›ื• ื–ืžืŸ ืงืฆืจ )ืคื—ื•ืช ืžืฉื ื”(. ืคืจืง ื–ืžืŸ ื›ื–ื” ืœื ืžืกืคื™ืง ื›ื“ื™ ืœื‘ื“ื•ืง ืฉื™ื ื•ื™ื™ื ื”ื™ืกื˜ื•ืœื•ื’ื™ื™ื ืฉืืžื•ืจื™ื ืœื—ื•ืœ ื‘ืขืงื‘ื•ืช ื™ืจื™ื“ื” ื‘ืชื ื’ื•ื“ืช ืœืื™ื ืกื•ืœื™ืŸ. ื”ืื ื™ืฉ ื”ื‘ื“ืœ ื‘ื™ืŸ ื”ื’ืœื™ื˜ื–ื•ื ื™ื ื”ืฉื•ื ื™ื? ืœื ื‘ืจื•ืจ. ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ ื”ื•ื‘ื™ืœ ืœืฉื™ืคื•ืจ ื‘ืจื•ื‘ ื‘โ€“2 ื”ืฉื™ืžื•ืฉ ืขื ื™ืจื“ื” ALTโ€“ื” ืจืžืช ื”ื”ื™ืกื˜ื•ืœื•ื’ื™ื™ื. ื”ืคืจืžื˜ืจื™ื ื’ื ื‘ืฉื™ืžื•ืฉ ื ืฆืคืชื” ืœื™ืจื™ื“ื” ื‘ืจืžืช ื”ืื ื–ื™ื ื–ื”ื” ื™ืจื™ื“ื” ื”ืชืจื•ืคื•ืช.

.E ื‘ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ ื•ื’ื ื‘ืฉื™ืžื•ืฉ ื‘ื•ื•ื™ื˜ืžื™ืŸืจืง 2 ืžื—ืงืจื™ื ื”ืฉื•ื• ื‘ื™ืŸ ืžื˜ืคื•ืจืžื™ืŸ ืœืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ. ืฉื ื™ื”ื ื›ืœืœื• ืžืกืคืจ ืงื˜ืŸ ืฉืœ ืžื˜ื•ืคืœื™ื, ื•ืœื›ืŸ ืœื ื ื™ืชืŸ ืœืงื‘ื•ืข ืขืœ ื‘ืกื™ืกื ืื™ื–ื• ืชืจื•ืคื” ืขื“ื™ืคื”,

ืื ื‘ื›ืœืœ.

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ืžืจืฅ 2012

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”ื ื™

ืžืฉื•

ื“ ื›ื‘

ื‘ื•ืœ

ื™ืคื˜

ื‘ืžื—ืœืช ื”ื ื–ืง ืžื ื’ื ื•ืŸ ื‘ื‘ืกื™ืก ืขื•ืžื“ืช ืœืื™ื ืกื•ืœื™ืŸ ืขืžื™ื“ื•ืช ื”ืงื“ืžื”: ื”ื›ื‘ื“ ื”ืฉื•ืžื ื™ ืฉืื™ื ื ื• ืขืœ ืจืงืข ืืœื›ื•ื”ื•ืœ, ื•ืžื›ืืŸ ืฉืชืจื•ืคื•ืช ื”ืžืขืœื•ืช ืืช ื”ืจื’ื™ืฉื•ืช ืœืื™ื ืกื•ืœื™ืŸ ื”ืŸ ืžื•ืขืžื“ื•ืช ื˜ื‘ืขื™ื•ืช ืœื ื™ืกื™ื•ืŸ ื˜ื™ืคื•ืœ ื‘ืžื—ืœืช ื”ื›ื‘ื“ ืžืชืžืงื“ื™ื ื‘ื ื•ืฉื ื”ืžื—ืงืจื™ื ืžืจื‘ ืืœื›ื•ื”ื•ืœ. ืจืงืข ืขืœ ืฉืœื ื”ืฉื•ืžื ื™ ื‘ืžื˜ืคื•ืจืžื™ืŸ )ื‘ื™ื’ื•ืื ื™ื“ื™ื( ื•ื‘ื˜ื™ืื–ื•ืœื™ื“ื™ื ื“ื™ื•ื ื™ื. ื‘ืกืงื™ืจื” ืฉืคื•ืจืกืžื” ืœืคื ื™ ื”ืจื’ื™ืฉื•ืช ืืช ื”ืžืขืœื•ืช ื‘ืชืจื•ืคื•ืช ื”ื˜ื™ืคื•ืœ ื™ืขื™ืœื•ืช ื ื‘ื—ื ื” ื›ื—ื•ื“ืฉื™ื™ื

ืœืื™ื ืกื•ืœื™ืŸ ื‘ืงืจื‘ ื—ื•ืœื™ ื›ื‘ื“ ืฉื•ืžื ื™. INSULIN ืžืกื•ื’ ื‘ืชืจื•ืคื•ืช ื”ืฉื™ืžื•ืฉ ืืช ืœืกืงื•ืจ ื•ืฉื™ื˜ื•ืช: ืžื˜ืจื”

SENSITIZER ืœื˜ื™ืคื•ืœ ื‘ื›ื‘ื“ ืฉื•ืžื ื™ ืฉืœื ืขืœ ืจืงืข ืืœื›ื•ื”ื•ืœ.

ืฉื™ื˜ื•ืช: ื ืขืฉืชื” ืกืงื™ืจื” ืฉื™ื˜ืชื™ืช ืฉืœ ืžืื’ืจื™ ืžื™ื“ืข ืžืžื•ื—ืฉื‘ื™ื ื•ื ื‘ื“ืงื” ื™ืขื™ืœื•ืชื ืฉืœ ืžื˜ืคื•ืจืžื™ืŸ, ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื•ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ.

ืžื”ื 4 ืžื‘ื•ืงืจื™ื. ืืงืจืื™ื™ื ืงืœื™ื ื™ื™ื ืžื—ืงืจื™ื 15 ืื•ืชืจื• ืชื•ืฆืื•ืช: ื‘ื“ืงื• ืืช ื”ื™ืขื™ืœื•ืช ืฉืœ ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ, ืื—ื“ ื‘ื—ืŸ ืืช ื”ื™ืขื™ืœื•ืช ืฉืœ ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ, ืžื˜ืคื•ืจืžื™ืŸ ื‘ื™ืŸ ื”ืฉื•ื• ืžื—ืงืจื™ื ื•ื‘โ€“2 ืžื˜ืคื•ืจืžื™ืŸ, ืฉืœ ื”ื™ืขื™ืœื•ืช ืืช 8

ืœืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ.

ืจื•ื‘ ื”ืžื—ืงืจื™ื ื ืžืฉื›ื• 6 ืขื“ 12 ื—ื•ื“ืฉื™ื ื•ืจื•ื‘ื ื›ืœืœื• ืžืกืคืจ ืงื˜ืŸ ืฉืœ ื ื‘ื“ืงื™ื )ื‘ื™ืŸ 8 ืœโ€“70 ื ื‘ื“ืงื™ื, ืœืžืขื˜ ืžื—ืงืจ ืื—ื“ ืฉื›ืœืœ 250 ื—ื•ืœื™ื(.

ืžื˜ืคื•ืจืžื™ืŸ8 ืžื—ืงืจื™ื ื‘ื“ืงื• ืžื˜ืคื•ืจืžื™ืŸ. ื‘โ€“5 ืžื”ื ื ืขื–ืจื• ื‘ื‘ื™ื•ืคืกื™ื•ืช ื›ื‘ื“, ื•ื‘ืฉืืจ ื‘ืกื•ื ืจ ื›ื‘ื“ ื‘ืœื‘ื“. ื‘ืจื•ื‘ ื”ืžื—ืงืจื™ื ืœื ื ืžืฆื ืฉื™ืคื•ืจ ืžืฉืžืขื•ืชื™ ื‘ืขืงื‘ื•ืช ืชื•ืกืคืช ืžื˜ืคื•ืจืžื™ืŸ ืœื“ื™ืื˜ื” ืื• ืœืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ. ื‘โ€“2 ืžื—ืงืจื™ื ื ืžืฆื ืฉื™ืคื•ืจ ื‘ื›ืžื•ืช ื”ืฉื•ืžืŸ ื‘ื›ื‘ื“ ื‘ืชื•ืฆืื•ืช ื‘ื“ื™ืงืช ืกื•ื ืจ ื•ื‘โ€“2 ืื—ืจื™ื ืœื ื ืจืื• ืฉื™ื ื•ื™ื™ื ื‘ื‘ื“ื™ืงืช ืกื•ื ืจ. ื‘โ€“2 ืžื—ืงืจื™ื ืฉื”ืฉื•ื• ื‘ื™ืŸ ืžื˜ืคื•ืจืžื™ืŸ ืœืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ืžืฉืžืขื•ืชื™ ืฉื™ืคื•ืจ ื”ื™ื” ืื—ื“ ื‘ืžื—ืงืจ ืžืขื•ืจื‘ื•ืช. ืชื•ืฆืื•ืช ื”ืชืงื‘ืœื• ื‘ื”ื™ืกื˜ื•ืœื•ื’ื™ื” ืจืง ื›ืืฉืจ ื—ื™ื‘ืจื• ืืช ืงื‘ื•ืฆืช ื”ืžื˜ืคื•ืจืžื™ืŸ ืœืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื™ื—ืกื™ืช ืœืงื‘ื•ืฆืช ื”ื‘ื™ืงื•ืจืช )ื“ื™ืื˜ื” ื‘ืœื‘ื“(, ื•ื‘ืžื—ืงืจ ื”ืฉื ื™ ื ืžืฆื ืฉื™ืคื•ืจ ื‘ืงื‘ื•ืฆืช ื”ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื•ื‘ืงื‘ื•ืฆื” ื”ืžืขื•ืจื‘ืช, ืืš ืœื ื‘ืงื‘ื•ืฆื” ืฉืงื™ื‘ืœื” ื‘ืžืชืŸ ืžื˜ืคื•ืจืžื™ืŸ. ALTโ€“ื” ื‘ืจืžืช ื™ืจื™ื“ื” ื ืžืฆืื” ื‘ืœื‘ื“. ืžื˜ืคื•ืจืžื™ืŸ ืฉื™ืžื•ืฉ ื‘ืžื˜ืคื•ืจืžื™ืŸ ืœื ื”ื•ื‘ื™ืœ ืœืฉื™ืคื•ืจ ื”ื™ืกื˜ื•ืœื•ื’ื™, ืืš ื›ืŸ ื ืจืืชื” ื™ืจื™ื“ื” ื’ื“ื•ืœื” ื™ื•ืชืจ ื‘ืจืžืช ื”ื”ืžื•ื’ืœื•ื‘ื™ืŸ ื”ืžืกื•ื›ืจ ื•ื‘ืจืžืช ื”ืกื•ื›ืจ ื‘ืฆื•ื ืœืขื•ืžืช

ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ. ืืฆืœ ื—ื•ืœื™ื ืฉื˜ื•ืคืœื• ื‘ืžื˜ืคื•ืจืžื™ืŸ ื ืจืืชื” ื™ืจื™ื“ื” ืงืœื” ื‘ืžืฉืงืœ ืฉืœ 4.3 ืง"ื’ ืขื“ 6.7 ืง"ื’ ืœืขื•ืžืช ื—ื•ืœื™ื ืฉื˜ื•ืคืœื• ื‘ืคื™ื•ื’ืœื™ื˜ื–ื•ืŸ. ื™ืฉ ืœืฆื™ื™ืŸ ื›ื™ ื”ื™ืขื“ืจ ืฉื™ืคื•ืจ ื‘ืขืงื‘ื•ืช ื˜ื™ืคื•ืœ ื‘ืžื˜ืคื•ืจืžื™ืŸ ื ื•ื‘ืข ื‘ืื•ืคืŸ ื—ืœืงื™ ืžืŸ ื”ืขื•ื‘ื“ื” ืฉื‘ื—ืœืง ืžื”ืžื—ืงืจื™ื ืžืฆื‘ื ืฉืœ ื”ืžื˜ื•ืคืœื™ื ื‘ื–ืจื•ืข ื”ื‘ื™ืงื•ืจืช ื”ืฉืชืคืจ

ื‘ืขืงื‘ื•ืช ื“ื™ืื˜ื”.

ื˜ื™ืื–ื•ืœื™ื“ื™ื ื“ื™ื•ื ื™ืืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื”ืžืชื•ืืจืช. ื‘ืกืงื™ืจื” ื ื‘ื“ืงื• ื–ื• ืžืงื‘ื•ืฆื” ืชืจื•ืคื•ืช 2

.)PROGLITAZONE( ื•ืคืจื•ื’ืœื™ื˜ื–ื•ืŸ )ROSIGLITAZONE(

ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸื‘ืžื—ืงืจ ื”โ€“FLRIT ืฉืชื•ืฆืื•ืชื™ื• ืคื•ืจืกืžื• ืœืคื ื™ ื›ืฉื ื”, ื ื‘ื“ืง ืžืชืŸ ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ืœืขื•ืžืช ืคืœืฆื‘ื• ื‘ืงืจื‘ 63 ืžื˜ื•ืคืœื™ื ืฉืกื‘ืœื• ืžื›ื‘ื“ ืฉื•ืžื ื™ ื‘ืžืฉืš ืฉื ื”. ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื ืจืื” ืฉื™ืคื•ืจ ื‘ืจืžืช ื”ืื ื–ื™ืžื™ื ืืฆืœ ืžื˜ื•ืคืœื™ื ืฉืงื™ื‘ืœื• ื•ื‘ืจื’ื™ืฉื•ืช ืœืื™ื ืกื•ืœื™ืŸ, ื•ื ืžืฆืื” ื™ืจื™ื“ื” ื‘ื›ืžื•ืช ื”ืฉื•ืžืŸ ื‘ื›ื‘ื“, ืืš ืœื ื—ืœ ืฉื™ื ื•ื™ ื‘ืžืจื›ื™ื‘ื™ื ื”ื”ื™ืกื˜ื•ืœื•ื’ื™ื™ื ื”ืื—ืจื™ื )ืžื“ื“ื™ ื“ืœืงืช ื•ืฆืœืงืช(. ื ื•ืกืฃ ืœื›ืš, ืจืง ื—ืฆื™ ืžื”ืžื˜ื•ืคืœื™ื ืฉืงื™ื‘ืœื• ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื”ื’ื™ื‘ื•. ื”ืžื—ืงืจ ื”ืจืื” ืฉื˜ื™ืคื•ืœ ื‘ื’ืœื™ื˜ื–ื•ื ื™ื ืœืœื ืฉื™ื ื•ื™ ื‘ืื•ืจื— ื”ื—ื™ื™ื ืื™ื ื• ื™ืขื™ืœ ื“ื™ื• ื‘ื˜ื™ืคื•ืœ ื‘ื›ื‘ื“ ืฉื•ืžื ื™ ืฉืœื ืขืœ ืจืงืข ืืœื›ื•ื”ื•ืœ. 53 ืžื˜ื•ืคืœื™ื ื”ืžืฉื™ื›ื• ื‘ืžื—ืงืจ ืฉื ืชื™ื™ื ื ื•ืกืคื•ืช )ืžื—ืงืจ FLIRT2(. ื‘ืžื”ืœืš ืฉื ืชื™ื™ื ืืœื• ืจืžืช ื”ืื™ื ืกื•ืœื™ืŸ ื‘ื“ื ื•ืจืžืช ื”โ€“ALT ื™ืจื“ื•, ืืš ืœื ื—ืœ ืฉื™ื ื•ื™ ืžืฉืžืขื•ืชื™ ื‘ืžื“ื“ื™ ื“ืœืงืช ื•ืฆืœืงืช ื™ืฉ ืฉืœืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื”ื™ื™ืชื” ื”ื—ื•ืงืจื™ื ื›ื‘ื“ื™ืช. ืžืกืงื ืช ื‘ื”ื™ืกื˜ื•ืœื•ื’ื™ื” ื”ืฉืคืขื” ืขืœ ื”ื•ืจื“ืช ืจืžืช ื”ืฉื•ืžืŸ ื‘ื›ื‘ื“ ื‘ืฉื ื” ื”ืจืืฉื•ื ื”, ืœืœื ื™ืชืจื•ืŸ ื ื•ืกืฃ ื‘ื˜ื™ืคื•ืœ ืืจื•ืš ื˜ื•ื•ื—, ืœืžืจื•ืช ื ืจืžื•ืœ ืจืžืช ALT ื•ืฉืžื™ืจื” ืขืœ ืจืžื” ื ืžื•ื›ื” ืฉืœ ืื™ื ืกื•ืœื™ืŸ. ืขื•ื‘ื“ื” ื–ื• ืจื•ืžื–ืช ืฉื˜ื™ืคื•ืœ ื‘ืขืžื™ื“ื•ืช ืœืื™ื ืกื•ืœื™ืŸ ืื™ื ื• ืžืกืคื™ืง ืขื‘ื•ืจ ื—ื•ืœื™ื ื”ืกื•ื‘ืœื™ื ืžื›ื‘ื“ ืฉื•ืžื ื™. ื™ืฉ ืœืฆื™ื™ืŸ ืฉื‘ืฉื ื” ื”ืื—ืจื•ื ื”

ื ืืกืจ ื”ืฉื™ืžื•ืฉ ื‘ืจื•ื–ื™ื’ืœื™ื˜ื–ื•ืŸ ื‘ืื™ืจื•ืคื”.

ื˜ื™ืคื•ืœ ื‘ื›ื‘ื“ ืฉื•ืžื ื™ ืฉืœื ืขืœ ืจืงืข ืืœื›ื•ื”ื•ืœ INSULIN SENSITIZER ื‘ืืžืฆืขื•ืช ืชืจื•ืคื•ืช ืžืกื•ื’

ืชื’ื•ื‘ื” ืœืžืืžืจ:Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic reviewShyangdan D, Clar C, Ghouri N, Henderson R, Gurung T, Preiss D, Sattar N, Fraser A, Waugh N Health Technol Assess. 2011 Nov; 15(38):1-110.

ื—ื ื™ ื™ืฉื•ืขื”1 ืฉื™ืจื” ื–ืœื‘ืจึพืฉื’ื™ื2,3

ืจืŸ ืื•ืจืŸ4 1ืฉื™ืจื•ืชื™ ื‘ืจื™ืื•ืช ื›ืœืœื™ืช, ื”ื™ื—ื™ื“ื” ืœืจืคื•ืืช ืžืฉืคื—ื”, ืžื—ื•ื– ืชืœ ืื‘ื™ื‘ึพื™ืคื•

2ื“ื™ืื˜ื ื™ืช ืงืœื™ื ื™ืช ื•ืืคื™ื“ืžื™ื•ืœื•ื’ื™ืช, ื”ืžื›ื•ืŸ ืœืžื—ืœื•ืช ื“ืจื›ื™ ื”ืขื™ื›ื•ืœ ื•ื”ื›ื‘ื“, ื”ืžืจื›ื– ื”ืจืคื•ืื™ ืชืœ ืื‘ื™ื‘, ืข"ืฉ ืกื•ืจืืกืงื™

3ื‘ื™ืช ื”ืกืคืจ ืœื‘ืจื™ืื•ืช ื”ืฆื™ื‘ื•ืจ, ื”ืคืงื•ืœื˜ื” ืœืžื“ืขื™ ื”ืจื•ื•ื—ื” ื•ื”ื‘ืจื™ืื•ืช, ืื•ื ื™ื‘ืจืกื™ื˜ืช ื—ื™ืคื”

4ื”ืžื›ื•ืŸ ืœื’ืกื˜ืจื•ืื ื˜ืจื•ืœื•ื’ื™ื” ื•ืžื—ืœื•ืช ื›ื‘ื“, ื‘ื™ืช ื”ื—ื•ืœื™ื ื”ืื•ื ื™ื‘ืจืกื™ื˜ืื™ ื”ื“ืกื”, ื™ืจื•ืฉืœื™ื

ื ื›ื•ืŸ ืœื”ื™ื•ื ืื™ืŸ ื”ืžืœืฆื” ืœื”ืฉืชืžืฉ ื‘ืื•ืคืŸ ืฉื’ืจืชื™ ื‘ืžื˜ืคื•ืจืžื™ืŸ ื‘ืงืจื‘ ืžื˜ื•ืคืœื™ื ื”ืกื•ื‘ืœื™ื ืžื›ื‘ื“ ืฉื•ืžื ื™ ืœืœื ืกื•ื›ืจืช.

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ืฉืœ ื”ื˜ื™ืคื•ืœ ื‘ืงืจื‘ ื›ืœ ื—ื•ืœื™ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื›ื‘ืจ ืคื•ืจื˜ื•. ืชื•ืคืขื•ืช ืœื•ื•ืื™ ืืœื” ืžืชื‘ื˜ืื•ืช ืœืขืชื™ื ื‘ืฆื•ืจื” ื—ืžื•ืจื” ื™ื•ืชืจ ืืฆืœ ื—ื•ืœื™ ื›ืœื™ื”. ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ืกื•ื‘ืœื™ื ื’ื ืžืกื™ื‘ื•ื›ื™ื ื™ื™ื—ื•ื“ื™ื™ื, ื”ื›ื•ืœืœื™ื ื‘ืฆืงืช ืจื™ืื•ืช, ื“ืœืงืช ืงืจื•ื ื”ืœื‘, ื™ืชืจ ืœื—ืฅโ€“ื“ื ื‘ืœืชื™ ื ืฉืœื˜, ืื™ืจื•ืขื™ ืžื•ื— ื“ื™ืžื•ืžื™ื™ื, ืคืจื›ื•ืกื™ื ืืคื™ืœืคื˜ื™ื™ื, ืฉื›ื™ื—ื•ืช ื’ื‘ื•ื”ื” ื™ื•ืชืจ ืฉืœ ื–ื™ื”ื•ืžื™ื ื•ืขื•ื“. ืชืžื•ื ืช ืžืฆื‘ ื–ื• ื”ื•ืคื›ืช ืืช ื”ื˜ื™ืคื•ืœ ื‘ืงื‘ื•ืฆืช ื—ื•ืœื™ื ื–ื• ืœื›ืžืขื˜ ื‘ืœืชื™ ืืคืฉืจื™ืช ืžื‘ื—ื™ื ื” ืžืขืฉื™ืช, ื•ืœืจืื™ื” ืฉื™ืขื•ืจื™ ื”ืคืกืงืช ื”ื˜ื™ืคื•ืœ ื”ื’ื‘ื•ื”ื™ื

ื‘ืกื“ืจื•ืช ื”ืฉื•ื ื•ืช.

ืกืงื™ืจืชื• ืฉืœ ื“"ืจ ืฉื™ื‘ื•ืœืช ืขืกืงื” ื‘ื˜ื™ืคื•ืœื™ื ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื‘ืงืจื‘ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื”ืžื•ืขืžื“ื™ื ืœื”ืฉืชืœืช ื›ืœื™ื”, ื•ื‘ื˜ื™ืคื•ืœื™ื ืœืื—ืจ ื”ื”ืฉืชืœื”. ื—ืฉื•ื‘ ืœื–ื›ื•ืจ ื›ื™ ื”ืคืจืžืงื•ืงื™ื ื˜ื™ืงื” ื•ื”ืคืจืžืงื•ื“ื™ื ืžื™ืงื” ืฉืœ ืื™ื ื˜ืจืคืจื•ืŸ ืœืฆื•ืจื•ืชื™ื• ื•ืฉืœ ืจื™ื‘ื•ื™ืจื™ืŸ ืฉื•ื ื” ื‘ืžืงืจื™ื ืฉืœ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ื•ืฉืœ ื“ื™ืืœื™ื–ื”. ื”ื•ืฆื’ื• ืฉื™ืขื•ืจื™ ื”โ€“SVR, ื”ืžืชืืคื™ื™ื ื™ื ื‘ืฉื•ื ื•ืช ืจื‘ื” )15% ืขื“ 75%( ื‘ืกื“ืจื•ืช ื”ืฉื•ื ื•ืช, ื•ื›ืŸ ื”ืฉื™ืขื•ืจ ื”ื’ื‘ื•ื” ืฉืœ ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื‘ืงืจื‘ ื—ื•ืœื™ื ืฉื˜ื•ืคืœื• ื‘ืื™ื ื˜ืจืคืจื•ืŸ ืจื’ื™ืœ ืื• ื‘โ€“Peg Interferon ื›ื˜ื™ืคื•ืœ ื™ื—ื™ื“, ืขื ืฉื™ืขื•ืจื™ ื”ืคืกืงืช ื˜ื™ืคื•ืœ ืฉืœ 30% ืขื“ 50%. ื‘ื˜ื™ืคื•ืœ ืžืฉื•ืœื‘ Peg Interferon ื•ืจื™ื‘ื•ื™ืจื™ืŸ ืœื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื ืฆืคื• ืฉืœ SVR ืฉืœ ื›โ€“56%, ืื•ืœื ื”ื—ื•ืงืจื™ื ืขื“ื™ื™ืŸ ื—ื•ืฉืฉื™ื ืœื”ืžืœื™ืฅ ืขืœ ืฉื™ืขื•ืจื™ ืžืชืŸ ืฉื’ืจืชื™ ืฉืœ ืฉื™ืœื•ื‘ ื–ื”, ื‘ืขื™ืงืจ ื‘ืฉืœ ื”ื•ืคืขืช ืื ืžื™ื” ืงืฉื” ืืฆืœ ื›ืจื‘ืข ืžื”ื—ื•ืœื™ื, ื’ื ื›ืืฉืจ ื ืขืฉื” ืฉื™ืžื•ืฉ ื‘ืžื™ื ื•ื ื™ื ื ืžื•ื›ื™ื ืžืื•ื“ ืฉืœ ืจื™ื‘ื•ื™ืจื™ืŸ. ื™ืฉ ืœื–ื›ื•ืจ ื›ื™ ื”ื—ื•ืœื™ื ืฉื ื“ื‘ืงื• ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื•ื ื›ืœืœื• ื‘ืกื“ืจื•ืช ื”ื˜ื™ืคื•ืœ ื”ื ืงื‘ื•ืฆื” ื ื‘ื—ืจืช ืžืื•ื“: ืžืจื‘ื™ืชื ื—ื•ืœื™ื ืžืชื—ืช ืœื’ื™ืœ 65 ืœืœื ืžื—ืœื•ืช ืจืงืข ืžืฉืžืขื•ืชื™ื•ืช, ื•ื‘ืขื™ืงืจ ืœืœื ืžื—ืœื•ืช ืงืจื“ื™ื•ื•ืกืงื•ืœืืจื™ื•ืช. ืจื•ื‘ ื”ื ื›ืœืœื™ื ื”ื™ื• ืžื•ืขืžื“ื™ื ืœื”ืฉืชืœืช ื›ืœื™ื”, ื•ืืฆืœ ืžืจื‘ื™ืชื ืœื ื”ื™ื™ืชื” ืขื“ื•ืช ืœืฉื—ืžืช ื”ื›ื‘ื“. ื“"ืจ ืฉื™ื‘ื•ืœืช ื”ื“ื’ื™ืฉ ืืช ื”ื”ืฉืคืขื” ื”ืฉืœื™ืœื™ืช ืฉื™ืฉ ืœื–ื™ื”ื•ื ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื‘ืงืจื‘ ืžื•ืฉืชืœื™ ื›ืœื™ื” ืขืœ ื”ื™ืฉืจื“ื•ืช ื”ืžืงื‘ืœ ื•ื”ืฉืชืœ. ื–ื™ื”ื•ื ื›ื–ื” ืืฃ ืžืขืœื” ืืช ืฉื›ื™ื—ื•ืช ื”ืชืคืชื—ื•ืชื” ืฉืœ Glomeruloathy, ืฉืœ ื ืคืจื•ืคืชื™ื•ืช ืื—ืจื•ืช ื•ืฉืœ ืกื•ื›ืจืช ืฉืœืื—ืจ ื”ืฉืชืœื”. ื ื•ืกืฃ ืœื›ืš, ื”ืฉืชืœืช ื›ืœื™ื” ืœื—ื•ืœื” ื”ืกื•ื‘ืœ ืžื–ื™ื”ื•ื ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ืขืœื•ืœื” ืœื”ื—ื™ืฉ ืืช ื”ื—ืžืจืช ื”ืžื—ืœื” ื‘ื›ื‘ื“. ื ืชื•ื ื™ื ืืœื• ื”ื ื”ื‘ืกื™ืก ืœื”ืžืœืฆื” ืขืœ ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื‘ืžื•ืขืžื“ื™ื ืœื”ืฉืชืœืช ื›ืœื™ื”. ื›ื™ื“ื•ืข, ื™ืฉ ื”ืชื•ื•ื™ื™ืช ื ื’ื“ ืœืฉื™ืžื•ืฉ ื‘ืื™ื ื˜ืจืคืจื•ืŸ ื‘ืงืจื‘ ืžื•ืฉืชืœื™ ื›ืœื™ื” ื‘ืฉืœ ืขืœื™ื™ื” ื‘ืฉื›ื™ื—ื•ืชื” ืฉืœ ื“ื—ื™ื™ื” ื—ืจื™ืคื” ืฉืœ ื”ืฉืชืœ ื”ืžื•ืคื™ืขื” ืืฆืœ 15% ืขื“ 64% ืžื”ืžื•ืฉืชืœื™ื ื‘ืกื“ืจื•ืช ื”ืฉื•ื ื•ืช. ืื•ืœื ื›ืืฉืจ ืžืชืคืชื—ืช ื“ืœืงืช Fibrosingโ€“ื›ื‘ื“ ื—ืจื™ืคื”, ื”ืžืœื•ื•ื” ื‘ืขื•ืžืก ื ื’ื™ืคื™ ื’ื‘ื•ื” ืžืื•ื“, ื›ืคื™ ืฉืงื•ืจื” ื‘Cholestatic Hepatitis, ื˜ื™ืคื•ืœ ื”ืžื›ื™ืœ ืื™ื ื˜ืจืคืจื•ืŸ ื”ื•ื ืืคืฉืจื•ืช ื”ื˜ื™ืคื•ืœ ื”ื™ื—ื™ื“ื” ื”ื–ื•ื›ื” ืœืฉื™ืขื•ืจื™ ื”ืฆืœื—ื” ืžืกื•ื™ืžื™ื. ื”ื™ื” ืžืื•ื“ ืžืขื ื™ื™ืŸ ื•ืืคื™ืœื• ืžืฉื•ื ื” ืœื“ื‘ืจ ืขืœ ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื‘ื–ืจื™ืงื•ืช ืื™ื ื˜ืจืคืจื•ืŸ ืจื’ื™ืœ ื‘ื›ื ืก ืฉื ืขืจืš ื‘ืฉื ืช 2011, ื›ืืฉืจ ื‘ืขืช ื›ืชื™ื‘ืช ืฉื•ืจื•ืช ืืœื” ื›ื‘ืจ ืื•ืฉืจ Direct Acting Anti-viralsโ€“ืฆื™ืจื•ืคื ืฉืœ ืชื›ืฉื™ืจื™ื ืคื•ืžื™ื™ื ืžืžืฉืคื—ืช ื”

ื )DAA( ืœืกืœโ€“ื”ืชืจื•ืคื•ืช. ืืžื ื ื”ื‘ืขื™ื” ื”ืžืจื›ื–ื™ืช ื‘ืงืจื‘ ื‘ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื”ื™ื ื–ื™ื”ื•ื ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C, ืื•ืœื ืฉื™ืขื•ืจ ื—ื•ืœื™ ื”ื“ื™ืืœื™ื–ื” ื”ื ื“ื‘ืงื™ื ื–ื ื™ื— ื›ืœืœ, ื‘ืขื™ืงืจ ื‘ืงืจื‘ ื—ื•ืœื™ื ื”ื—ื™ื™ื B ืื™ื ื• ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ื‘ืžื“ื™ื ื•ืช ืžืชืคืชื—ื•ืช )ื›โ€“10% ืžื—ื•ืœื™ ื”ื“ื™ืืœื™ื–ื”(. ื”ืžื”ืœืš ื”ื˜ื‘ืขื™ ืฉืœ ื–ื™ื”ื•ื ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช B ืื™ื ื• ื‘ืจื•ืจ ื“ื™ ืฆื•ืจื›ื• ื•ื–ื™ื”ื•ื ืžืฉื•ืœื‘ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ืื• ื‘โ€“HIV, ืฉืงื•ืจื” ืœืขืชื™ื ืœื ื ื“ื™ืจื•ืช, ื™ื›ื•ืœ ื›ืžื•ื‘ืŸ ืœืฉื ื•ืช ืžื”ืœืš ื–ื”. ื—ื•ืœื™ ื“ื™ืืœื™ื–ื” ืฆืคื•ื™ื™ื ืœืกื‘ื•ืœ ืžืชื—ืœื•ืื” ื•ืžืชืžื•ืชื” ื‘ืฉื™ืขื•ืจื™ื

ื’ื‘ื•ื”ื™ื ื™ื•ืชืจ ืžื”ืฉื™ืขื•ืจื™ื ื‘ืื•ื›ืœื•ืกื™ื™ื” ื”ื›ืœืœื™ืช, ืœื›ืŸ ื‘ืžืจื‘ื™ืช ื”ืžื—ืงืจื™ื ืฉืขืกืงื• ื‘ื ื•ืฉื )ืจื•ื‘ื ื›ื›ื•ืœื ืจื˜ืจื•ืกืคืงื˜ื™ื‘ื™ื™ื(, ืœื ื ืฆืคืชื” ืขืœื™ื™ื” ืžืฉืžืขื•ืชื™ืช ื‘ืชืžื•ืชื” ืฉืœ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื” ืกื•ืคื ื™ืช ื•ื“ื™ืืœื™ื–ื” ื•ืฉืœ ืžื•ืฉืชืœื™ ื›ืœื™ื” ืฉื ื“ื‘ืงื• ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช B, ืœืขื•ืžืช ืืœื” ืœืœื ื–ื™ื”ื•ื. ืืคืฉืจื•ื™ื•ืช ื”ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช B ืจื‘ื•ืช ื™ื•ืชืจ, ื•ื›ื•ืœืœื•ืช ื›ื™ื“ื•ืข ื›ืžื” Nucleos(t)ide Analogues, ืืš ื”ืžื™ื“ืข ื”ืงื™ื™ื ื‘ื™ื“ื™ื ื• ืœื’ื‘ื™ ื˜ื™ืคื•ืœ ื‘ืื•ื›ืœื•ืกื™ื™ืช ื—ื•ืœื™ ื”ื›ืœื™ื” ื”ื•ื ื“ืœ ื•ืžืžื•ืงื“ ื‘ื˜ื™ืคื•ืœ ื‘โ€“Lamivudine ื‘ืœื‘ื“. ื™ืฉ ืœื–ื›ื•ืจ ื›ื™ ืžืชืŸ ื”ืชืจื•ืคื•ืช ืฆืจื™ืš ืœื”ื™ื•ืช ืžื•ืชืื ืœืชืคืงื•ื“ ื”ื›ืœื™ื•ืช, ื•ืœื—ื•ืœื™ ื“ื™ืืœื™ื–ื” ื”ื•ื ื ื™ืชืŸ ืœืื—ืจ ื˜ื™ืคื•ืœ ื‘ื“ื™ืืœื™ื–ื” 3 ืคืขืžื™ื ื‘ืฉื‘ื•ืข. ืงื™ื™ืžืช ื”ืžืœืฆื” ื—ื“ ืžืฉืžืขื™ืช ืœื˜ืคืœ ื‘ื—ื•ืœื™ื ื”ืžืžืชื™ื ื™ื ืœื”ืฉืชืœืช ื›ืœื™ื” ื•ืกื•ื‘ืœื™ื ืžื–ื™ื”ื•ื ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช B ื•ืขื“ื•ืช ืœืจืคืœืงืฆื™ื”. ืœืขื•ืžืช ื–ืืช, ืœื’ื‘ื™ ื—ื•ืœื™ื ื”ืžื˜ื•ืคืœื™ื ื‘ื“ื™ืืœื™ื–ื” ื•ืื™ื ื ืžื•ืขืžื“ื™ื ืœื”ืฉืชืœื”, ื”ื”ื—ืœื˜ื” ื‘ื™ืŸ ืฆืจื™ื›ื” ืœื”ืชืงื‘ืœ ืขืœ ืคื™ ืฉื™ืงื•ืœื™ ืกื™ื›ื•ืŸ/ืชื•ืขืœืช ืขื‘ื•ืจ ื›ืœ ื—ื•ืœื”. ื”ืฉื™ืงื•ืœื™ื ื™ืฉ ืœืžื ื•ืช ืคื’ื™ืขื” ืคื•ื˜ื ืฆื™ืืœื™ืช ื‘ื›ืœื™ื•ืช ื›ืชื•ืฆืื” ืžื”ืฉื™ืžื•ืฉ ื•ื”ื•ืจื“ืช ื•ื”ื•ืคืขืช ืขืžื™ื“ื•ืช ืฉืœ ื”ื ื’ื™ืฃ ืœื˜ื™ืคื•ืœ ืžืฆื“ ืื—ื“, ื‘ืชืจื•ืคื•ืช B ื‘ืชื•ืš ื™ื—ื™ื“ื•ืช ื”ื“ื™ืืœื™ื–ื” ืฉื™ืขื•ืจื™ ื”ื”ืขื‘ืจื” ืฉืœ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช

ืžืฆื“ ืฉื ื™. ืœื”ื’ื‘ืจืช ืžื•ื‘ื™ืœื” ื•ื›ื‘ื“ ื›ืœื™ื” ืชืจื•ืžื•ืช ืฉืœ ื”ืžื•ื’ื‘ืœืช ื”ื–ืžื™ื ื•ืช ื”ื ื™ืกื™ื•ื ื•ืช ืœื”ืจื—ื™ื‘ ืืช ืžืื’ืจ ื”ืชื•ืจืžื™ื ืขืœโ€“ื™ื“ื™ ืฉื™ืžื•ืฉ ื‘ืชืจื•ืžื•ืช ืžื ืฉืื™ )+Hepatitis B Core Antibodies )HBcAb ื•ืžื ืฉืื™ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ืขื‘ื•ืจ ืžืงื‘ืœื™ื ื”ืกื•ื‘ืœื™ื ืžื–ื™ื”ื•ื ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C. ืื ืžื“ื•ื‘ืจ HBcAb- ืื• HBcAb+ ืœืžืงื‘ืœื™ื ืฉื”ื HBcAb+ ื‘ืชืจื•ืžื•ืช ื›ืœื™ื” ืžื ืฉืื™ื–ื™ื”ื•ื +HBsAg, ืืคืฉืจ ืœืžื ื•ืข ื”ื™ืฉื ื•ืช ืื• ื”ื•ืคืขื” ืฉืœ +HBsAg, ืื• Nucleos)t(ide Analogues Lamivudine ืื• B ื‘ืืžืฆืขื•ืช ื‘ื”ืคื˜ื™ื˜ื™ืก ืื—ืจื™ื. ื‘ืžืงืจื™ื ืžืกื•ื™ืžื™ื ืจืฆื•ื™ ืืฃ ืœื ืกื•ืช ืœื—ืกืŸ ืืช ื”ืžืงื‘ืœื™ื ืžืคื ื™ B ื›ืฉื ื” ืœืื—ืจ ื”ื”ืฉืชืœื”. ืชืจื•ืžืช ื›ืœื™ื” ืžืชื•ืจื ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ,C ื ื’ื™ืคื™ืช ื—ื™ื•ื‘ื™ ืœื“ืœืงืช ื›ื‘ื“ C ืœืžืงื‘ืœ ื ื’ื™ืคื™ืช ื—ื™ื•ื‘ื™ ืœื“ืœืงืช ื›ื‘ื“ ืื™ื ื” ืžืฉืคื™ืขื” ืขืœ ื”ื™ืฉืจื“ื•ืช ื”ืžืงื‘ืœ ืื• ื”ืฉืชืœ, ืืš ืžืขืœื” ืืช ื”ืกื™ื›ื•ืŸ ืœื”ื•ืคืขืช ืื™โ€“ืกืคื™ืงืช ื›ื‘ื“ ืœืื—ืจ ื”ื”ืฉืชืœื”. ืœื›ืŸ ื™ืฉ ืฆื•ืจืš ืœื‘ื—ื•ืจ ื”ื™ื˜ื‘ ืืช ื”ืžืงื‘ืœื™ื ื•ืœื”ื™ืžื ืข ืœืžืฉืœ ืžืžืชืŸ ืชืจื•ืžื” ืžื ืฉื ื”ืคื˜ื™ื˜ื™ืก C ืœืžืงื‘ืœ ืขื RNA ืฉืœื™ืœื™, ื•ื›ืŸ ืœื”ืงืคื™ื“ ืœื”ืชืื™ื ืืช ื”ื’ื ื•ื˜ื™ืค ืฉืœ ื”ืชื•ืจื ืœื–ื” ืฉืœ

ื”ืžืงื‘ืœ.

ืœืกื™ื›ื•ืืžืืจื’ื ื™ ื”ื›ื ืก ืžืฉืชื™ ื”ื—ื‘ืจื•ืช ื”ืžืงืฆื•ืขื™ื•ืช ืจืื•ื™ื™ื ืœืฉื‘ื—ื™ื ืขืœ ืืจื’ื•ืŸ ื•ื ื™ื”ื•ืœ ื”ื›ื ืก. ื”ื›ื ืก ื”ื™ื” ืžืงื™ืฃ ืžื‘ื—ื™ื ืช ืžื’ื•ื•ืŸ ื”ื ื•ืฉืื™ื ื‘ื•, ื•ื”ื ื•ืฉืื™ื ื”ื•ืฆื’ื• ื‘ืจืžื” ื’ื‘ื•ื”ื” ื‘ื™ื•ืชืจ. ืื ื™ ืžืฆืคื” ืœื›ื ืกื™ื ื”ืžืฉื•ืชืคื™ื ื”ื‘ืื™ื

ื‘ื ื•ืฉืื™ื ืžื’ื•ื•ื ื™ื ืื—ืจื™ื.

ื™ื“ื•ืข ื›ื™ ื‘ืงืจื‘ ื—ื•ืœื™ ืื™ึพืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื•ื“ื™ืืœื™ื–ื” ื ืฆืคื•ืช ืจืžื•ืช ืืžื™ื ื•ื˜ืจื ืกืคืจื–ื•ืช โ€œื ืžื•ื›ื•ืช" ื™ื—ืกื™ืช, ื’ื ื‘ืžืงืจื™ื ืฉืœ ืžื—ืœื•ืช

ื›ื‘ื“ ื›ื’ื•ืŸ ื–ื™ื”ื•ื ื›ืจื•ื ื™ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช.ืคืจื•ืค' Angeli ื”ื“ื’ื™ืฉ ืืช ื—ืฉื™ื‘ื•ืช ื”ื™ืจื™ื“ื” ื‘ืชืคื•ืงืช ื”ืœื‘ ื‘ืคืชื•ื’ื ื–ื” HRS ื”ื ื’ืจื ื›ืชื•ืฆืื” ืžืคืจื™ึพ ึพืœืœ ื”ืชืกืžื•ื ืช ื”ื”ืคื˜ื•ืจื ืœื™ืช, ื‘ืขื™ืงืจ ื‘

ื˜ื•ื ื™ื˜ื™ืก ื—ื™ื™ื“ืงื™ืช ืจืืฉื•ื ื™ืช ืื• ืžื–ื™ื”ื•ื ืื—ืจ. ื”ื™ืจื™ื“ื” ื‘ืชืคื•ืงืช ื”ืœื‘ ื”ื™ื ืชื•ืฆืื” ืฉืœ ืฉื™ืœื•ื‘ ื‘ื™ืŸ ื™ืจื™ื“ื” ื‘ื”ื—ื–ืจ ื”ื•ื•ืจื™ื“ื™ ืืœ ื”ืœื‘

ืœื‘ื™ืŸ ื™ืจื™ื“ื” ื‘ื›ื•ืฉืจ ื”ื”ืชื›ื•ื•ืฆื•ืช ืฉืœ ืฉืจื™ืจ ื”ืœื‘

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ืžืจืฅ 2012

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”ืก

ื›ื ืžื”

ื ืžื™

ืฉื•ืจ

ื ื ื™

ื›ื•ืขื“

)Tubular Injury( ืงืฉื” ื–ื•. ื‘ื›ืžื” ืžื—ืงืจื™ื ื ืžืฆื ื ื–ืง ืœืื‘ื•ื‘ื™ื•ืช ื”ื›ืœื™ื”ื‘ืงืจื‘ ื—ื•ืœื™ื ื”ืกื•ื‘ืœื™ื ืžืชืกืžื•ื ืช ื”ืคื˜ื•ืจื ืœื™ืช, ื“ื”ื™ื™ื ื•, ื”ื›ืœื™ื” ืกื•ื‘ืœืช Acute Tubular ืžื ื–ืง ืฉืื™ื ื• ืชืคืงื•ื“ื™ ื‘ืœื‘ื“ ื•ืขืœื•ืœื” ืœืคืชื— ืคื’ื™ืขื” ื“ืžื•ื™ืชATN( Necrosis( ืฉืื™ื ื” ื”ืคื™ื›ื”. ืœืžืžืฆืื™ื ืืœื” ื”ืฉืœื›ื•ืช ืขืœ ื”ืฆื•ืจืš ื‘ื‘ื™ืฆื•ืข ื”ืฉืชืœื” ืžืฉื•ืœื‘ืช ืฉืœ ื›ื‘ื“ ื•ื›ืœื™ื” ื‘ืงืจื‘ ื—ื•ืœื™ื ื‘ืžื—ืœืช ื›ื‘ื“

ืกื•ืคื ื™ืช. ื ื•ืฉื ื–ื” ื ืกืงืจ ื‘ื™ืชืจ ื”ืจื—ื‘ื” ืขืœโ€“ื™ื“ื™ ื“"ืจ ื‘ืจืื•ืŸ. ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ื‘ืงืจื‘ ืžื•ืขืžื“ื™ื ืœื”ืฉืชืœืช ื›ื‘ื“ ื›ืจื•ื›ื” ื‘ื™ืจื™ื“ื” ื‘ื”ื™ืฉืจื“ื•ืช ืฉืœ ื”ืžื•ืฉืชืœ ื•ืฉืœ ื”ืฉืชืœ, ื•ืžืœื•ื•ื” ื’ื ื‘ืฉื™ืขื•ืจื™ื ื’ื‘ื•ื”ื™ื ืฉืœ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืœืื—ืจ ื”ื”ืฉืชืœื”. ืืฆืœ ื—ื•ืœื™ื ื”ืžื˜ื•ืคืœื™ื ื‘ื“ื™ืืœื™ื–ื” ื‘ืฉืœ AKI, ื”ืฉืชืœื” ืžืฉื•ืœื‘ืช ืฉืœ ื›ื‘ื“ ื•ื›ืœื™ื” ืžื‘ื˜ื™ื—ื” ื”ื™ืฉืจื“ื•ืช ื’ื‘ื•ื”ื” ื™ื•ืชืจ ืžืืฉืจ ื”ืฉืชืœืช ื›ื‘ื“ ื‘ืœื‘ื“. ืœื›ืŸ, ืœืคื™ ื”ื”ืžืœืฆื•ืช ื”ืžืงื•ื‘ืœื•ืช, ืžื•ืขืžื“ื™ื ืœื”ืฉืชืœืช ื›ื‘ื“ ืขื ืงืจื™ืื˜ื™ื ื™ืŸ ื’ื‘ื•ื” ืžโ€“2 ืž"ื’ ืœื“"ืœ ื”ืžื˜ื•ืคืœื™ื ื‘ื“ื™ืืœื™ื–ื” ื‘ืžืฉืš 8 ืฉื‘ื•ืขื•ืช ื•ื™ื•ืชืจ, ืฆืจื™ื›ื™ื ืœืขื‘ื•ืจ ื”ืฉืชืœืช ื›ื‘ื“ ื•ื›ืœื™ื” ืžืฉื•ืœื‘ืช. ืžื•ืขืžื“ื™ื ื”ืœื•ืงื™ื Glomerular( ืคืงืขื™ืชื™ ืกื™ื ื•ืŸ ืงืฆื‘ ืขื ื›ืจื•ื ื™ืช ื›ืœื™ื•ืช ื‘ืื™โ€“ืกืคื™ืงืช ื–ืงื•ืงื™ื ืืฃ ื”ื Filtration Rate - GFR( ื”ื ืžื•ืš ืžโ€“30 ืž"ืœ ืœื“ืงื”, ืœื”ืฉืชืœื” ืžืฉื•ืœื‘ืช. ืœืžื•ืขืžื“ื™ื ืœื”ืฉืชืœื” ืฉื”โ€“GFR ืฉืœื”ื ื ืข ื‘ื™ืŸ 30 ืœโ€“60 ืž"ืœ ืœื“ืงื” ื ื—ื•ืฆื” ื”ืขืจื›ื” ืžื“ื•ืงื“ืงืช, ื”ื›ื•ืœืœืช ื‘ื™ื•ืคืกื™ื™ืช ื›ืœื™ื”. ื”ื‘ื™ื•ืคืกื™ื” ืžืืคืฉืจืช ืื‘ื—ื ื” ืžื“ื•ื™ืงืช ื›ืืฉืจ ืžืชืขื•ืจืจ ื—ืฉื“ ืœืžื—ืœืช ื›ืœื™ื” ืจืืฉื•ื ื™ืช, ืื• ื›ืืฉืจ ื™ืฉ ืื™โ€“ื•ื“ืื•ืช ื‘ืืฉืจ ืœื™ื›ื•ืœืช ื”ืฉื™ืคื•ืจ ื‘ืชืคืงื•ื“ ื”ื›ืœื™ื•ืช ืœืื—ืจ ื”ืฉืชืœืช ื”ื›ื‘ื“. ืžืžืฆืื™ื ืฉืœ Interstitial Fibrosis ืžืขืœ 30% ื•โ€“Glomerular Sclerosis ืžืขืœ 30% ื‘ื‘ื™ื•ืคืกื™ื”, ื”ื ื”ื•ืจื™ื” ืœื”ืฉืชืœื”

ืžืฉื•ืœื‘ืช.

ื”ื•ื ืกื™ืงื•ืœืจ. ืคืจื•ืคืกื•ืจ ืกื™ื›ื ืขืœ ื”ื›ืœื™ื” ืืช ืคืจืง ื”ืฉืคืขืช ื”ื›ื‘ื“ ืขืžื“ ื‘ืจืืฉ ื•ืขื“ื” ืฉื’ื™ื‘ืฉื” ืืช ื”ื”ื ื—ื™ื•ืช ื”ื™ืฉืจืืœื™ื•ืช ืœื˜ื™ืคื•ืœ ื‘ื—ื•ืœื™ ืฉื—ืžืช ื”ืกื•ื‘ืœื™ื ืžืžื™ื™ืžืช, ืคืจื™ื˜ื•ื ื™ื˜ื™ืก ื—ื™ื™ื“ืงื™ืช ืจืืฉื•ื ื™ืช ื•ืชืกืžื•ื ืช ื”ื—ื‘ืจื” ื‘ืืชืจ ืœืžืฆื•ื ื ื™ืชืŸ ื‘ืžืœื•ืืŸ ื”ื”ืžืœืฆื•ืช ืืช ื”ืคื˜ื•ืจื ืœื™ืช.

ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“. ื™ื“ื•ืข ื›ื™ ื‘ืงืจื‘ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื•ื“ื™ืืœื™ื–ื” ื ืฆืคื•ืช ืจืžื•ืช ืื ื’ื ื™ื—ืกื™ืช, โ€œื ืžื•ื›ื•ืช" )Aminotransferase( ืืžื™ื ื•ื˜ืจื ืกืคืจื–ื•ืช ื”ืžื˜ื•ืคืœื™ื ืกื•ื‘ืœื™ื ืžืžื—ืœื•ืช ื›ื‘ื“ ื›ื’ื•ืŸ ื–ื™ื”ื•ื ื›ืจื•ื ื™ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช )ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช(. ื“"ืจ ืœื•ื™ืŸโ€“ื™ื™ื ื” ืกื™ื›ืžื” ืืช ื”ืกืคืจื•ืช ื‘ื ื•ื’ืข ืœืจืžืช ื”ืืžื™ื ื•ื˜ืจื ืกืคืจื–ื•ืช ื•ืื ื–ื™ืžื™ ื”ื›ื‘ื“ ื”ืื—ืจื™ื ื‘ืงืจื‘ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื•ื“ื™ืืœื™ื–ื”. ื ืกืงืจื• ื”ืืคืฉืจื•ื™ื•ืช ื”ืคืชื•ื’ื ื˜ื™ื•ืช ื”ืฉื•ื ื•ืช ื›ื’ื•ืŸ ื”ืฉืคืขืช ืจืขืœืŸ ืื•ืจืžื™ )Uremic Toxin( ื•ื—ื•ืกืจ ื‘ื•ื•ื™ื˜ืžื™ืŸ B6, ื•ื‘ืขื™ืงืจ ื”ืžื˜ื‘ื•ืœื™ืช Pyridoxal-5-phosphate, ืขืœ ืจืžืช ื”ืืžื™ื ื•ื˜ืจื ืกืคืจื–ื•ืช. ื”ืคืขื™ืœ ืฉืœื• ืจืžื•ืช ALT ื•โ€“AST ื ืžื•ื›ื•ืช ื‘ืงืจื‘ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื•ื“ื™ืืœื™ื–ื” ืžื—ื™ื™ื‘ื•ืช ื”ื•ืจื“ื” ืฉืœ โ€œืขืจื›ื™ ื”ื ื•ืจืžื”" ืฉืœ ืื ื–ื™ืžื™ื ืืœื” ื›ื“ื™ ืœืืคืฉืจ ืœื”ืขืœื•ืช ืืช ื”ืจื’ื™ืฉื•ืช ืœืื‘ื—ื•ืŸ ืžื—ืœื•ืช ื›ื‘ื“ ื•ื‘ืขื™ืงืจ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช. Gamma- ื”ื•ืฆื’ื” ื’ื ืชืฆืคื™ืช ืžืขื ื™ื™ื ืช, ืฉืขืœ ืคื™ื” ืขืœื™ื™ื” ื‘ืจืžืช ื”ืื ื–ื™ืฮณ-GGT( Glutamyl Transpeptidase( ื”ื™ื ืกืžืŸ ื—ื–ืง ื•ื‘ืœืชื™ ืชืœื•ื™ ืœืชืžื•ืชื”

ื›ืœืœื™ืช ื•ืงืจื“ื™ื•ื•ืกืงื•ืœืืจื™ืช ื‘ืงืจื‘ ื—ื•ืœื™ ื“ื™ืืœื™ื–ื”.

ืžืžื™ืœื ื• ืื™ื˜ืœื™ื”, Fabrizi ืืช ื—ืœืงื• ื”ืฉื ื™ ืฉืœ ื”ื›ื ืก ืคืชื— ืคืจื•ืคืกื•ืจ ืžืžื•ื‘ื™ืœื™ ื”ืžื—ืงืจ ื‘ืชื—ื•ื ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื•ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื‘ื”ืจืฆืืชื• ื”ืจืืฉื•ื ื” ื”ืฆื™ื’ ืืช ื”ืงืฉืจ ื‘ื™ืŸ ื–ื™ื”ื•ื ื‘ื”ืคื˜ื™ื˜ื™ืก .Cโ€“ื• B ,)Membranoproliferative Glomerulonephritis( ืœืžื—ืœืช ื›ืœื™ื” ืจืืฉื•ื ื™ืชืืช ืฉื›ื™ื—ื•ืชื”, ืืช ื“ืจื›ื™ ืื‘ื—ื•ื ื” ื•ืืช ืฆื•ืจื•ืช ื”ื˜ื™ืคื•ืœ ื”ืฉื•ื ื•ืช ื‘ื”. ื›ื™ื“ื•ืข, Essential Mixed - ืžื—ืœื” ื–ื• ื”ื™ื ืื—ื“ ื”ื‘ื™ื˜ื•ื™ื™ื ืฉืœ ืงืจื™ืื•ื’ืœื•ื‘ื•ืœื™ื ืžื™ื”Cryoglobulinemia. ื‘ื”ืจืฆืื” ืžืฉืœื™ืžื” ืกืงืจ ืคืจื•ืคืกื•ืจ ืฆื•ืงืจืžืŸ ืืช C ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช B ื”ืจืฆืฃ ืฉื—ืœ ืขื ื”ื“ื‘ืงืช ืœื™ืžืคื•ืฆื™ื˜ื™ื ืžืกื•ื’

ื•ื”ืชื™ื™ื—ืก ืœื•ื•ื™ืกื•ืช ื”ืœืงื•ื™ ืฉืœ ืžืขืจื›ืช ื”ื—ื™ืกื•ืŸ ืขื ืฉื’ืฉื•ื’ ืฉืœ ืœื™ืžืคื•ืฆื™ื˜ื™ื ื”ื•ืคืขืช ืชื™ืชื›ืŸ ื‘ื”ืžืฉืš ืงืจื™ืื•ื’ืœื•ื‘ื•ืœื™ื ื™ื. ืฉืžืคืจื™ืฉื™ื ,B ืžืกื•ื’ ื”ืชืžืจื•ืช ื’ื ื˜ื™ื•ืช, ื”ืขืœื•ืœื•ืช, ืœืขืชื™ื ืจื—ื•ืงื•ืช, ืœื”ื•ื‘ื™ืœ ืœื”ื•ืคืขืช ืžื—ืœื•ืช ืœื™ืžืคื•ืคืจื•ืœื™ืคืจื˜ื™ื‘ื™ื•ืช. ื”ืงืจื™ืื•ื’ืœื•ื‘ื•ืœื™ื ื™ื ืฉื•ืงืขื™ื ื‘ืฆื•ืจืช ืžื›ืœื•ืœื™ื ื•ื—ืœืงื™ืงื™ื ืื—ืจื™ื ืฉืœ ื”ื ื’ื™ืฃ ื‘ื“ื•ืคื ื•ืช ื—ื™ืกื•ื ื™ื™ื ืขื ื”โ€“RNA ื”ื ื’ื™ืคื™ ืงืœื™ื ื™ื•ืช ื‘ืชื•ืคืขื•ืช ื–ื• ืฉืงื™ืขื” ืžืœื•ื•ื” ืžื”ื—ื•ืœื™ื ื—ืœืง ืืฆืœ ื“ื. ื›ืœื™ ื ื’ืขื™ื ื‘ืขื•ืจ ื›ื•ืœืœื•ืช ื•ืกืงื•ืœื™ื˜ื™ืก. ืชื•ืคืขื•ืช ืืœื” ืจื‘โ€“ืžืขืจื›ืชื™ื•ืช ืฉืœ ื›ื’ื•ืŸ Reynaud syndrome, ื›ื™ื‘ื™ื ืงืฉื™ื, ื“ืœืงืช ืžืคืจืงื™ื, ื ืื•ืจื•ืคืชื™ื” ืคืจื™ืคืจื™ืช ื•ืขื•ื“. ื›ืืžื•ืจ, ื”ืคื’ื™ืขื” ื”ื›ืœื™ื™ืชื™ืช ืžืชื‘ื˜ืืช ื‘ืžืจื‘ื™ืช ื”ืžืงืจื™ื

.Membranoproliferative Glomerulonephritisโ€“ื‘ื‘ื”ืจืฆืื” ื”ื•ืฆื’ื• ืฉื ื™ ื”ื›ื™ื•ื•ื ื™ื ื”ืขื™ืงืจื™ื™ื ืœื˜ื™ืคื•ืœ ื‘ืžื—ืœื” ื–ื•: ื”ืจืืฉื•ืŸ .C ื”ื•ื ื˜ื™ืคื•ืœ ื‘ืžื—ื•ืœืœ ื”ื–ื™ื”ื•ื - ื“ื”ื™ื™ื ื• ื ื™ืกื™ื•ืŸ ืœืกืœืง ืืช ื”ื”ืคื˜ื™ื˜ื™ืก Sustained Viral(ื SVR - ื‘ืงืจื‘ ื—ื•ืœื™ื ืฉื”ืฉื™ื’ื• ืชื’ื•ื‘ื” ื ื’ื™ืคื™ืช ืžื•ืฉื”ื™ืชResponse(, ื ืฆืคืชื” ื’ื ืชื’ื•ื‘ื” ืงืœื™ื ื™ืช ืฉืœ ื”ืงืจื™ืื•ื’ืœื•ื‘ื•ืœื™ื ืžื™ื”. ืขื ื–ืืช, ืœื ืชืžื™ื“ ื ืžืฆื ืžืชืื ื‘ื™ืŸ ื”ืคื•ื’ืช ื”ืžื—ืœื” ืœื‘ื™ืŸ ืกื™ืœื•ืง ื”ื ื’ื™ืฃ. ืขื“ ืงืœื” ื‘ืžื—ืœื” ืจืง ื”ืื ื˜ื™โ€“ื ื’ื™ืคื™ ืœื˜ื™ืคื•ืœ ืžืงื•ื ื™ืฉ ื›ื™ ืœื–ื›ื•ืจ ื™ืฉ ,B ื‘ื™ื ื•ื ื™ืช. ื›ื™ื•ื•ืŸ ืคืขื•ืœื” ืฉื ื™ ื”ื•ื ื˜ื™ืคื•ืœ ื‘ืฉื’ืฉื•ื’ ื”ืœื™ืžืคื•ืฆื™ื˜ื™ื ืžืกื•ื’ื•ืชืจื•ืคืช ื”ื‘ื—ื™ืจื” ื”ื™ื Retuximab, ื ื•ื’ื“ืŸ ื—ื“โ€“ืฉื‘ื˜ื™ ืœืœื™ืžืคื•ืฆื™ื˜ื™ื ืžืกื•ื’ Monoclonal Anti-CD20 - B. ื‘ื˜ื™ืคื•ืœ ื‘โ€“Retuximab ื‘ืžืฉื˜ืจื™ื ืฉื•ื ื™ื ื ืฆืคืชื” ืชื’ื•ื‘ื” ืงืœื™ื ื™ืช ื‘ืฉื™ืขื•ืจ ืฉืœ 50% ืขื“ 85% ื‘ื”ืชืื ืœืฆื•ืจื•ืช ื”ื”ืชื‘ื˜ืื•ืช ื”ืฉื•ื ื•ืช ืฉืœ ื”ืงืจื™ืื•ื’ืœื•ื‘ื•ืœื™ื ืžื™ื”, ื›ื•ืœืœ ื‘ืžืงืจื™ื ืฉืœ ืคื’ื™ืขื” ื ื•ื™ืจื•ืœื•ื’ื™ืช ื•ื›ืœื™ื™ืชื™ืช, ื”ื ื—ืฉื‘ื™ื ืœืขืžื™ื“ื™ื ืœื˜ื™ืคื•ืœ. ื™ืฉ ืœื–ื›ื•ืจ ื›ื™ ื”ืคื•ื’ืช ื”ืžื—ืœื” ื™ื›ื•ืœื” ืœื”ืชืจื—ืฉ ื—ื•ื“ืฉื™ื ืจื‘ื™ื ืœืื—ืจ ื”ื˜ื™ืคื•ืœ, ื•ื›ื™ ื™ืฉ ื ื˜ื™ื™ื” ืœื”ื™ืฉื ื•ืช ื”ืžื—ืœื”. ื‘ืฉืœ ื ื˜ื™ื™ื” ืœืขืœื™ื™ื” ื‘ืขื•ืžืก ื”ื ื’ื™ืคื™ ืฉืœ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ื‘ืงืจื‘ ื—ื•ืœื™ื ื”ืžื’ื™ื‘ื™ื ืœื˜ื™ืคื•ืœ, ืžื•ืžืœืฅ ืœืฉืœื‘ ืืช ืžืชืŸ ื”โ€“

Retuximab ื‘ื˜ื™ืคื•ืœ ื ื’ื“ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ืขื Peg Interferon ื•ืขื ืจื™ื‘ื•ื™ืจื™ืŸ. ื™ืฉ ืœื”ื“ื’ื™ืฉ ื›ื™ ื”ื˜ื™ืคื•ืœ ื‘โ€“Retuximab ื™ืขื™ืœ ื‘ืžืงืจื™ื ืฉืœ ืžื—ืœื” ื‘ื™ื ื•ื ื™ืช ื™ืฆื™ื‘ื”, ื•ืื™ืœื• ื‘ืžืงืจื™ื ื—ืžื•ืจื™ื ื™ื•ืชืจ ื›ื’ื•ืŸ ืžื—ืœื” ื›ืœื™ื™ืชื™ืช ื“ื•ื”ืจืช

ื™ืฉ ืœื ืงื•ื˜ ื‘ืืžืฆืขื™ ื˜ื™ืคื•ืœ ืื—ืจื™ื. ื“"ืจ ืจื•ืžื™ ืžืžื—ืœืงืชื• ืฉืœ ืคืจื•ืคืกื•ืจ ืกื™ืงื•ืœืจ ื”ืฆื™ื’ื” ืคืจืฉืช ืžืงืจื” ืžืืชื’ืจืช ืฉืœ ื—ื•ืœื” ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C ืฉืคื™ืชื— ืชืกืžื•ื ืช ื ืคืจื•ื˜ื™ืช ื—ื“ื” ื‘ืžื”ืœืš ื”ื˜ื™ืคื•ืœ ื”ืžืงื•ื‘ืœ ืœืžื—ืœืชื•. ืžืงืจื” ื–ื” ืžื“ื’ื™ื ืฉื•ื‘ ืขื“ ื›ืžื”

ื—ืฉื•ื‘ โ€œืœื—ืฉื•ื‘ ืžื—ื•ืฅ ืœืงื•ืคืกื”" ื›ืืฉืจ ืžื˜ืคืœื™ื ื‘ืชืจื•ืคื•ืช. ื‘ืžื”ืœืš ื”ื›ื ืก ื ืขืจืš ืขื™ืžื•ืช ื‘ื™ืŸ ื“"ืจ ืงืจื•ื–ืŸ, ื ืคืจื•ืœื•ื’ื™ืช ืฉืžืฉื™ืžืชื” ื”ื™ื™ืชื” ืœื”ื™ื•ืช ืคืจืงืœื™ื˜ืช ื”ื˜ื™ืคื•ืœ ื”ืื ื˜ื™โ€“ื ื’ื™ืคื™ ื‘ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื•ื“ื™ืืœื™ื–ื” ืœื‘ื™ืŸ ื”ื—ืชื•ื ืžื˜ื” ืฉื”ืฆื™ื’ ืขืžื“ื” ื”ืคื•ื›ื”. ื”ื“ื™ื•ืŸ ื”ืชื‘ืกืก KDIGO - Kidney Disease Improving Globalโ€“ื‘ืขื™ืงืจ ืขืœ ื”ืžืœืฆื•ืช ื”Outcome1, ื•ื’ื ืขืœ ืžืืžืจื™ื ืžื”ืฉื ื” ื”ืื—ืจื•ื ื”. ืœืฆืขืจื ื•, ืžืกืžืš ื–ื” ื”ื•ื

C ืขื“ื™ื™ืŸ ื”ื‘ืกื™ืก ื”ืžืงื™ืฃ ื”ื™ื—ื™ื“ ืœื”ื—ืœื˜ื•ืช ืขืœ ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืชื‘ืงืจื‘ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช. ืžืกืงื™ืจืชื” ื”ืžืงืคืช ืฉืœ ื“"ืจ ืงืจื•ื–ืŸ ื ื™ืชืŸ ื”ื™ื” ืœื”ืชืจืฉื ื›ื™ ืื™ืŸ ืชืžื™ื›ื” ืžื—ืงืจื™ืช ืžืกืคืงืช ืœื”ืžืœืฆื” ื’ื•ืจืคืช ืœื˜ืคืœ ื‘ื›ืœ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื”ื›ืœื™ื•ืช ื”ืกื•ืคื ื™ืช ืฉื ื“ื‘ืงื• ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช C, ื”ื™ื•ืช ืฉื”ื˜ื™ืคื•ืœ ื›ืจื•ืš ื‘ืชื•ืคืขื•ืช ืœื•ื•ืื™ ืžืฉืžืขื•ืชื™ื•ืช ื•ืื™ื ื• ืžืฉืคืจ ืืช ืžืฆื‘ ื”ืชื—ืœื•ืื” ื•ืืช ืฉื™ืขื•ืจ ื”ืชืžื•ืชื” ื‘ืงืจื‘ ื—ื•ืœื™ื ืืœื”. ืขื ื–ืืช, ืืฆืœ ื—ื•ืœื™ื ื”ืžื•ืขืžื“ื™ื ืœื”ืฉืชืœืช ื›ืœื™ื•ืช, ืจืื•ื™ ื›ื™ ื™ื™ืขืฉื” ืžืืžืฅ ืœืกื™ืœื•ืง

ื”ื ื’ื™ืฃ, ืฉื›ืŸ ื”ื•ื›ื— ื›ื™ ืกื™ืœื•ืงื• ืžืฉืคืจ ืืช ื”ื™ืฉืจื“ื•ืช ื”ื—ื•ืœื” ื•ื”ืฉืชืœ. ืœืขื•ืžืชื”, ื”ื—ืชื•ื ืžื˜ื” ื™ื™ืฆื’ ืขืžื“ื” ื”ืžืชื ื’ื“ืช ืœื˜ื™ืคื•ืœ ื‘ื—ื•ืœื™ื ืืœื” ื‘ืื™ื ื˜ืจืคืจื•ืŸ ื•ื‘ืจื™ื‘ื•ื™ืจื™ืŸ. ื”ื”ืฉืงืคื” ืžืชื‘ืกืกืช ืขืœ ืฉื™ืขื•ืจื™ ื”ืชื—ืœื•ืื” ื•ื”ืชืžื•ืชื” ื”ืžืฉืžืขื•ืชื™ื™ื ืฉืœ ื—ื•ืœื™ ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ื•ื“ื™ืืœื™ื–ื”. ืžืจื‘ื™ืช ืžืงืจื™ ื”ืชื—ืœื•ืื” ื•ื”ืชืžื•ืชื” ืžืฉื ื™ื™ื ืœืกื™ื‘ื•ื›ื™ื ืงืจื“ื™ื•ื•ืกืงื•ืœืืจื™ื™ื, ื•ืžื™ืขื•ื˜ื ื‘ืœื‘ื“ ืžืฉื ื™ื™ื ืœืžื—ืœืช ื›ื‘ื“ ืžืชืงื“ืžืช. ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื”ืงืฉื•ืช

)Suppl. 109: S20-S45 Kidney International( 73 ;20081ืคื•ืจืกืžื• ื‘ึพ

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ื—ื•ื“ืฉ ืกืคื˜ืžื‘ืจ ื”ืื—ืจื•ืŸ ื”ืชืงื™ื™ื ื›ื ืก ื—ื“โ€“ื™ื•ืžื™ ืฉืœ ื”ื—ื‘ืจื” ื‘ื•ื”ื•ืคื›ืช ืฉื”ื•ืœื›ืช ื‘ืžืชื›ื•ื ืช ื›ื‘ื“ ืœืžื—ืœื•ืช ื”ื™ืฉืจืืœื™ืช ื›ื‘ื“ ืœืžื—ืœื•ืช ื”ืžื•ืžื—ื™ื ื™ื•ืฆืื™ื ืืœื” ื‘ื›ื ืกื™ื ืงื‘ื•ืขื”. ื•ื”ื’ืกื˜ืจื•ืื ื˜ืจื•ืœื•ื’ื™ื ืžืืจื‘ืข ื”ืืžื•ืช ืฉืœื”ื ื•ื™ื•ืฆืจื™ื ืงืฉืจ ื‘ืœืชื™ ืืžืฆืขื™ ืขื ืžื•ืžื—ื™ื ืžืชื—ื•ืžื™ื ืื—ืจื™ื, ื”ืžืฉื™ืงื™ื ื•ืœืขืชื™ื ืืฃ ื—ื•ืคืคื™ื ืœืžื—ืœื•ืช ื”ื›ื‘ื“ ื•ื“ืจื›ื™ ื”ืžืจื” ื”ืฉื•ื ื•ืช. ื›ื ืกื™ื ืืœื” ื”ืชืงื‘ืœื• ืขื“ ื›ื” ื‘ืื”ื“ื” ืจื‘ื”, ืฉื›ืŸ ื ืงื•ื“ื•ืช ื”ื”ืฉืงืคื” ืฉืœ ืžื•ืžื—ื™ื ืžืชื—ื•ืžื™ื ืื—ืจื™ื ืžืขืฉื™ืจื•ืช ื”ืŸ ืืช

ืžื•ืžื—ื™ ื”ื›ื‘ื“ ื•ื”ืŸ ืืช ืืœื” ื”ืขื•ืกืงื™ื ื‘ืฉื˜ื—ื™ ื”ืจืคื•ืื” ื”ืื—ืจื™ื.ื”ืฉื ื” ื”ืชืžืงื“ ื”ื›ื ืก ื‘ืงืฉืจ ืฉื‘ื™ืŸ ื”ื›ื‘ื“ ืœื›ืœื™ื”, ื•ื ื“ื•ื ื• ื‘ื”ืจื—ื‘ื” ืฉืชื™ ื ืงื•ื“ื•ืช ืžืžืฉืง ืขื™ืงืจื™ื•ืช ื‘ื™ืŸ ื”ืžืขืจื›ื•ืช. ื‘ื—ืœืง ื”ืจืืฉื•ืŸ ืฉืœ ื”ื›ื ืก ืขืกืงื• ื”ื”ืจืฆืื•ืช ื‘ืงืฉืจ, ื”ืžื•ื›ืจ ืœื”ืคื˜ื•ืœื•ื’ื™ื ื•ืœื ืคืจื•ืœื•ื’ื™ื, ื‘ื™ืŸ ืฉื—ืžืช ื”ื›ื‘ื“ ืœื‘ื™ืŸ ื”ืคืจืขื” ื‘ืชืคืงื•ื“ ื”ื›ืœื™ื”. ื—ืœืงื• ื”ืฉื ื™ ืฉืœ ื”ื›ื™ื ื•ืก ืขืกืง ื‘ื’ื™ืฉื” ืœื—ื•ืœื™

.Cโ€“ื• B ืื™โ€“ืกืคื™ืงืช ื›ืœื™ื•ืช ืกื•ืคื ื™ืช ืฉื ื“ื‘ืงื• ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืชื‘ื‘ืชื™ ื”ื—ื•ืœื™ื ื ืชืงืœื™ื ืžื“ื™ ื™ื•ื ื‘ื—ื•ืœื™ ืฉื—ืžืช ืžืชืงื“ืžืช ื”ืžืคืชื—ื™ื ื”ื˜ื™ืคื•ืœ ื•ื“ืจื›ื™ ื‘ื›ืœื™ื•ืช ืœื”ืคืจืขื” ื”ืกื™ื‘ื” ืื‘ื—ื•ืŸ ื›ืœื™ื•ืช. ืื™โ€“ืกืคื™ืงืช

ื”ืฉื•ื ื•ืช ื”ื ื ื•ืฉืื™ื ืœื“ื™ื•ืŸ, ื•ืœืขืชื™ื ื”ื ืžืงื•ืจ ืœื—ื™ืœื•ืงื™ ืžืฉื ื™ ืžื•ืžื—ื™ื ื‘ื™ืŸ ื“ืขื•ืช ื• ืชื™ ื”ืจืฆืื• ื. ืžื™ ื”ืชื—ื• A n g el i ืจ ืคืจื•ืคืกื• ืฉืœ ืฉื”ื•ื ืื™ื˜ืœื™ื”, ืžืคื“ื•ื‘ื” ื”ืžื•ื‘ื™ืœื™ื ื”ื—ื•ืงืจื™ื ืื—ื“ ื‘ืชื—ื•ื, ื™ืฆืจื• ื‘ืกื™ืก ืžืฉื•ืชืฃ ืœืฉืชื™ ื”ื—ื‘ืจื•ืช ื”ืžืงืฆื•ืขื™ื•ืช ื‘ื ื•ืฉืื™ื ื”ื‘ืื™ื: ื”ื’ื“ืจื•ืช ื ื™ ื‘ ืฆ ืž ืœ ืช ื• ืž ื› ืก ื• ืžื”ื ื—ืช ื”ืฉื•ื ื™ื, ื”ืงืœื™ื ื™ื™ื ืขื“ื›ื ื™ืช ืœื”ื‘ื ื” ื”ืชืฉืชื™ืช

ืฉืœ ื”ืคืชื•ืคื™ื–ื™ื•ืœื•ื’ื™ื” ืฉืœ ืžื—ืœืช ื”ื›ืœื™ื•ืช ืฉืžืžื ื” ืกื•ื‘ืœื™ื ื—ื•ืœื™ ืฉื—ืžืช ื”ื›ื‘ื“, ื•ืœื‘ืกื•ืฃ ื”ื’ื™ืฉื•ืช ื”ื—ื“ืฉื•ืช ืœื˜ื™ืคื•ืœ ื‘ืžื™ื™ืžืช, ื‘ืคืจื™ื˜ื•ื ื™ื˜ื™ืก ื—ื™ื™ื“ืงื™ืช Spontaneous Bacterial Peritonitisื )SBP( ื•ื‘ืชืกืžื•ื ืช ืจืืฉื•ื ื™ืช - ื”ื”ืคื˜ื•ืจื ืœื™ืช - Hepatorenal Syndromeื )HRS(. ื’ื™ืฉื•ืช ืืœื• ืžื‘ื•ืกืกื•ืช

ืขืœ ื”ื‘ื ื” ืžื ื’ื ื•ื ื™ืช.

ืžื”ืจืฆืื•ืชื™ื• ืฉืœ Angeli ืจืื•ื™ ืœื”ื–ื›ื™ืจ ืืช ื”ืขื ื™ื™ื ื™ื ื”ื‘ืื™ื: ืžื•ืžื—ื™ ื›ื‘ื“ )Acute Kidney Injury - AKI( ื•ื ืคืจื•ืœื•ื’ื™ื ืžื’ื“ื™ืจื™ื ื ื–ืง ื—ืจื™ืฃ ืœื›ืœื™ื•ืชื‘ืงืจื‘ ื—ื•ืœื™ ืžื—ืœืช ื›ื‘ื“ ืกื•ืคื ื™ืช ื‘ืื•ืคืŸ ืฉื•ื ื”. ื‘ืขื™ืงืจ ื ื•ื’ืข ื”ื“ื‘ืจ ืœื”ื’ื“ืจืช ื”ืžืฆื‘ ืœืคื™ ื”ื”ืคื˜ื•ืœื•ื’ื™ื. ืœื”ื’ื“ืจืชื, ืคื’ื™ืขื” ื›ื–ื• ืžืชื‘ื˜ืืช ื‘ืขืจืš ืžื•ื—ืœื˜ ืฉืœ ืงืจื™ืื˜ื™ื ื™ืŸ ืžืขืœ ืœโ€“1.5 ืž"ื’ ืœื“"ืœ. ืœืขื•ืžืช ื”ื”ื’ื“ืจื•ืช ื”ื”ืคื˜ื•ืœื•ื’ื™ื•ืช, ืฉื™ืžื•ืฉ ื‘ื”ื’ื“ืจื•ืช ื”ื ืคืจื•ืœื•ื’ื™ื•ืช ืจื’ื™ืฉ ื™ื•ืชืจ ื•ืžื ื‘ื ื˜ื•ื‘ ื™ื•ืชืจ ืืช ื”ืชืžื•ืชื”

ืชื•ืš 3 ื—ื•ื“ืฉื™ื. ืœื›ืŸ, ืจืฆื•ื™ ืฉื”ื—ื‘ืจื” ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“ ืชืืžืฅ ื”ื’ื“ืจื•ืช ืืœื”.

Bacterial ื”โ€“ ืชืคืงื™ื“ ืœื”ื‘ื ืช ื”ื•ืงื“ืฉ ืžื”ื”ืจืฆืื” ื ื›ื‘ื“ ื—ืœืง Translocation ืฉืœ ื—ื™ื™ื“ืงื™ื ืžื—ืœืœ ื”ืžืขื™ ืœืงืฉืจื™ื•ืช ื”ืœื™ืžืคื” ื”ืžื–ื ื˜ืจื™ื•ืช )Mesenteric Lymph Nodes( ื‘ื”ืชื”ื•ื•ืช ืกื™ื‘ื•ื›ื™ ืฉื—ืžืช ื”ื›ื‘ื“. ืื—ื“ ื”ืกืžื ื™ื ื”ื—ืœื•ืคื™ื™ื ืœืื‘ื—ื•ืŸ ืžืขื‘ืจ ืฉืœ ื—ื™ื™ื“ืงื™ื ื‘ื”ื™ืขื“ืจ SBP, ื”ื•ื ื‘ื“ื™ืงื” ืœืื™ืชื•ืจ DNA ื—ื™ื™ื“ืงื™ )Bacterial DNA( ื‘ืกืจื•ื ืื• ื‘ื ื•ื–ืœ ื”ืžื™ื™ืžืช. ื‘ืงืจื‘ ื ื‘ื“ืงื™ื ืฉืื•ืชืจ ืืฆืœื DNA ื—ื™ื™ื“ืงื™ ื ืฆืคื• ืจืžื•ืช ื’ื‘ื•ื”ื•ืช ืžืฉืžืขื•ืชื™ืช ืฉืœ ืื ื“ื•ื˜ื•ืงืกื™ื ื™ื )Endotoxins(, ืจืžื•ืช ื’ื‘ื•ื”ื•ืช ื™ื•ืชืจ ื‘ืกืจื•ื ื•ื‘ื ื•ื–ืœ )Proinflammatory Cytokines( ื”ืžื™ื™ืžืช ืฉืœ ืฆื™ื˜ื•ืงื™ื ื™ื ืžืขื•ื“ื“ื™โ€“ื“ืœืงืช )NO(ื Nitric Oxide ื•ื™ื™ืฆื•ืจ ืžื•ื’ื‘ืจ ืฉืœ ืžืจื—ื™ื‘ื™ ื›ืœื™ ื“ื ื›ื’ื•ืŸ ,TNF-ฮฑ ื›ื’ื•ืŸืขืœโ€“ื™ื“ื™ ืชืื™ื ืžืืงืจื•ืคื’ื™ื ื‘ื—ืœืœ ื”ืฆืคืง, ืœืขื•ืžืช ื—ื•ืœื™ื ืฉืืฆืœื ืœื ืื•ืชืจ DNA ื—ื™ื™ื“ืงื™ ื”ืชืืคื™ื™ื ื” ื‘ื”ืคืจืขื•ืช DNA ื—ื™ื™ื“ืงื™. ื ื•ืกืฃ ืœื›ืš, ื ื•ื›ื—ื•ืช ื”ืžื•ื“ื™ื ืžื™ื•ืช ื—ืžื•ืจื•ืช ื™ื•ืชืจ ื›ื’ื•ืŸ ืœื—ืฅโ€“ื“ื ืžืžื•ืฆืข ื ืžื•ืš ื™ื•ืชืจ ื•ืชื ื’ื•ื“ืช ืกื™ืกื˜ืžื™ืช ื ืžื•ื›ื” ื™ื•ืชืจ ืฉืœ ื›ืœื™โ€“ื”ื“ื. ื‘ืขื‘ื•ื“ื” ืžื•ืงื“ืžืช ื™ื•ืชืจ, ืฉื‘ื” ื˜ื•ืคืœื• ื—ื•ืœื™ ืฉื—ืžืช ื•ืžื™ื™ืžืช ืœืœื SBP ื‘โ€“Norfloxacin, ื ืจืืชื” ื™ืจื™ื“ื” ืžืฉืžืขื•ืชื™ืช ื‘ืจืžื•ืช ื”ืื ื“ื•ื˜ื•ืงืกื™ื ื™ื ื‘ืคืœื–ืžื” ื•ืขืœื™ื™ื” ืžืงื‘ื™ืœื” ื‘ืชื ื’ื•ื“ืช

ื›ืœื™ ื”ื“ื ืœืขื•ืžืช ื”ืขืจื›ื™ื ื”ื‘ืกื™ืกื™ื™ื.ื‘ื”ืจืฆืื•ืชื™ื• ื”ื“ื’ื™ืฉ ืคืจื•ืคืกื•ืจ Angeli ืืช ืžืฉืžืขื•ืช ื”ื™ืจื™ื“ื” ื‘ืชืคื•ืงืช ื”ืœื‘ ื‘ืคืชื•ื’ื ื–ื” ืฉืœ ื”ืชืกืžื•ื ืช ื”ื”ืคื˜ื•ืจื ืœื™ืช, ื‘ืขื™ืงืจ ืื ื–ื• ื ื’ืจืžืช ื›ืชื•ืฆืื” ืžืคืจื™ื˜ื•ื ื™ื˜ื™ืก ื—ื™ื™ื“ืงื™ืช ืจืืฉื•ื ื™ืช ืื• ืžื–ื™ื”ื•ื ืื—ืจ. ื”ื™ืจื™ื“ื” ื‘ืชืคื•ืงืช ื”ืœื‘ ื”ื™ื ืชื•ืฆืื” ืฉืœ ืฉื™ืœื•ื‘ ื‘ื™ืŸ ื™ืจื™ื“ื” ื‘ื”ื—ื–ืจ ื”ื•ื•ืจื™ื“ื™ ืืœ ื”ืœื‘ .)MyocardialContractility( ืœื™ืจื™ื“ื” ื‘ื›ื•ืฉืจ ื”ื”ืชื›ื•ื•ืฆื•ืช ืฉืœ ืฉืจื™ืจ ื”ืœื‘ื‘ืžื•ื“ืœื™ื ื‘ืžืขื‘ื“ื” ื”ื•ื“ื’ืžื” ื™ืจื™ื“ื” ื‘ื”ืชื›ื•ื•ืฆื•ืช ืฉืจื™ืจ ื”ืœื‘ ื‘ืชื™ื•ื•ืš ืฉืœ ื•โ€“Inducible NOื )iNOS(. ืžืขื ื™ื™ืŸ ืฉืžืชืŸ ืืœื‘ื•ืžื™ืŸ, ืฉื”ื•ื ื—ืœืง TNF-ฮฑืžื”ื˜ื™ืคื•ืœ ื”ืžืงื•ื‘ืœ ื‘โ€“HRS, ืฉื™ืคืจ ืืช ื”ืชื›ื•ื•ืฆื•ืช ืฉืจื™ืจ ื”ืœื‘ ื‘ืžื•ื“ืœื™ื ืชืกืžื•ื ืช ืฉืœ ื‘ืžืงืจื™ื ื ืฆืคื• ื”ืœื‘ ื‘ืชืคื•ืงืช ื“ื•ืžื™ื ืฉื™ื ื•ื™ื™ื ืืœื”. ื”ืคื˜ื•ืจื ืœื™ืช ื’ื ืœืœื ืขื“ื•ืช ืœื–ื™ื”ื•ื ื’ืœื•ื™. ื›ืœื•ืžืจ, ื™ื™ืชื›ืŸ ืฉืœื˜ืจื ืกืœื•ืงืฆื™ื”

ืฉืœ ื—ื™ื™ื“ืงื™ื ื™ืฉ ื”ืฉืœื›ื•ืช ืขืœ ื”ืคืชื•ื’ื ื–ื” ืฉืœ ื”ื”ืคืจืขื” ื”ืœื‘ื‘ื™ืช. Terlipressin ื‘โ€“HRS ื›ื•ืœืœ ืžืชืŸ ืชื•ืšโ€“ื•ืจื™ื“ื™ ืฉืœ ื”ื˜ื™ืคื•ืœ ื”ืžืงื•ื‘ืœ ื‘ืžื ื•ืช ื—ื•ื–ืจื•ืช ื‘ืฉื™ืœื•ื‘ ืขื ืชืžื™ืกืช ืืœื‘ื•ืžื™ืŸ ืชื•ืšโ€“ื•ืจื™ื“ื™ืช. ืžืฉื˜ืจ ื˜ื™ืคื•ืœ ื–ื” ืžื•ื‘ื™ืœ ืœืฉื™ืคื•ืจ ื‘ืชืคืงื•ื“ ื”ื›ืœื™ื•ืช ืืฆืœ ืคื—ื•ืช ืžืžื—ืฆื™ืช ื”ืžื˜ื•ืคืœื™ื ื‘ืœื‘ื“. ืœืื•ืจ ื”ืชื’ื•ื‘ื” ื”ืชืชโ€“ืžื™ื˜ื‘ื™ืช ืœื˜ื™ืคื•ืœ ื‘ืชืกืžื•ื ืช ื”ื”ืคื˜ื•ืจื ืœื™ืช, ื”ื•ื“ื’ืฉ ื”ืฆื•ืจืš ื‘ืžืฆื™ืืช ื’ื•ืจืžื™ื ื”ืžื ื‘ืื™ื ืชื’ื•ื‘ื” ืœื˜ื™ืคื•ืœ. ื‘ืžื—ืงืจื™ื ืฉื•ื ื™ื ื ืžืฆืื” ื”ืชืืžื” ื‘ื™ืŸ ืจืžืช ื”ื‘ื™ืœื™ืจื•ื‘ื™ืŸ, ืฉื™ืขื•ืจ ืขืœื™ื™ืช ื”โ€“MAP ืชื•ืš ื›ื“ื™ ื˜ื™ืคื•ืœ ื•ืจืžืช ื”ืงืจื™ืื˜ื™ื ื™ืŸ ื”ื‘ืกื™ืกื™ืช ืœื‘ื™ืŸ ื”ืชื’ื•ื‘ื” ืœื˜ื™ืคื•ืœ ื”ืžืงื•ื‘ืœ. HRSโ€“ื‘ื”ืกืชืžืš ืขืœ ื ืชื•ื ื™ื ืืœื” ื”ื•ื“ื’ืฉ ื”ืฆื•ืจืš ื‘ื”ืชื—ืœืช ื”ื˜ื™ืคื•ืœ ื‘ืžื•ืงื“ื ื›ื›ืœ ื”ื ื™ืชืŸ. ืœืžืจื•ืช ื”ื”ืชืงื“ืžื•ืช ืฉื ืขืฉืชื” ืขื“ ื›ื”, ื™ืฉ ืฆื•ืจืš ืœืžืฆื•ื ืžื“ื“ื™ื ื ื•ืกืคื™ื ืœื ื™ื‘ื•ื™ ื”ืชื’ื•ื‘ื”, ื•ื›ืžื•ื‘ืŸ ืฉื ื“ืจืฉื™ื ื˜ื™ืคื•ืœื™ื ื ื•ืกืคื™ื ื›ื’ื•ืŸ ืฉื™ืžื•ืฉ ื‘ืชื›ืฉื™ืจื™ื ืื™ื ื•ื˜ืจื•ืคื™ื™ื ืœืฉื™ืคื•ืจ ื”ืชื’ื•ื‘ื” ื‘ืงื‘ื•ืฆืช ื—ื•ืœื™ื

ืขื“ื›ื•ื ื™ื ื‘ืžื—ืœื•ืช ื›ื‘ื“ ืจืฉืžื™ื ืžื”ื›ื ืก ื”ื—ื“ึพื™ื•ืžื™ ืฉืœ ื”ื—ื‘ืจื” ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“ ื‘ืฉื™ืชื•ืฃ ืขื

ื”ืื™ื’ื•ื“ ื”ื™ืฉืจืืœื™ ืœื ืคืจื•ืœื•ื’ื™ื” - โ€œื”ื›ื‘ื“ ืคื•ื’ืฉ ืืช ื”ื›ืœื™ื”" - 6 ื‘ืกืคื˜ืžื‘ืจ 2011ื™ืขืงื‘ ืžืื•ืจ

ืจื•ืคื ื‘ื›ื™ืจ ื‘ืžื›ื•ืŸ ืœืžื—ืœื•ืช ื“ืจื›ื™ ื”ืขื™ื›ื•ืœ ื•ื”ื›ื‘ื“, ืฉื™ื‘ื, ืชืœ ื”ืฉื•ืžืจ

ื”ื™ืจื™ื“ื” ื‘ืชืคื•ืงืช ื”ืœื‘ ื”ื™ื ืชื•ืฆืื” ืฉืœ ืฉื™ืœื•ื‘ ื‘ื™ืŸ ื™ืจื™ื“ื” ื‘ื”ื—ื–ืจ ื”ื•ื•ืจื™ื“ื™ ืืœ ื”ืœื‘ ืœื™ืจื™ื“ื” ื‘ื›ื•ืฉืจ ื”ื”ืชื›ื•ื•ืฆื•ืช ืฉืœ ืฉืจื™ืจ ื”ืœื‘ .)MyocardialContractility(ื‘ืžื•ื“ืœื™ื ื‘ืžืขื‘ื“ื” ื”ื•ื“ื’ืžื” ื™ืจื™ื“ื” ื‘ื”ืชื›ื•ื•ืฆื•ืช ืฉืจื™ืจ ื”ืœื‘ TNF-ฮฑ ื‘ืชื™ื•ื•ืš ืฉืœ )iNOS(ื Inducible NOื•ึพ

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ื‘ืงืจื‘ ื”ื–ื”ืืคืฉืจ ืœื ืฆื—!

ื”ืขืชื™ื“ ื‘ื˜ื™ืคื•ืœ ื‘- HCV ื›ื‘ืจ ื›ืืŸื•ื›ืœื•ืœ ื‘ืกืœ ื”ื‘ืจื™ืื•ืช

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ื”ื”ืžืœืฆื” ื”ืžืงื•ื‘ืœืช ื”ื™ื•ื ]NEJM[ ื”ื™ื ืฉื™ืฉ ืœืขืจื•ืš ืกืจื™ืงื” ืœืื™ืชื•ืจ ืกืจื˜ืŸ ื”ื›ื‘ื“ ื‘ืขื–ืจืช ืกื•ื ืจ ื‘ื˜ืŸ ื•ืจืžืช AFP ืคืขื ื‘ึพ6 ืขื“ 12 ื—ื•ื“ืฉื™ื ืœื›ืœ ื—ื•ืœื™ ืฉื—ืžืช ื›ื‘ื“ ืื• ืคื™ื‘ืจื•ื–ื™ืก ืžืชืงื“ื, ืœืœื ืงืฉืจ ืœืžื—ืœืช ืจืงืข.

ื‘ืกืจื˜ืŸ ื”ื›ื‘ื“. ืžื•ื“ืœ BCLC ื”ื•ื ื›ืœื™ ื—ืฉื•ื‘ ื”ืžืฉืœื‘ ื”ืชื™ื™ื—ืกื•ืช ืœืžื“ื“ื™ ื•ื’ื•ื“ืœืŸ, ืœืชืกืžื™ื ื™ ืกืจื˜ืŸ ืžืฆื‘/ื‘ื™ืฆื•ืข ืฉืœ ื”ื—ื•ืœื”, ืœืžืกืคืจ ื”ืงืฉืจื™ื•ืช ื•ืœืชืคืงื•ื“ ื”ื›ื‘ื“, ื•ื”ื—ืœื•ืงื” ื ืงื‘ืขืช ื‘ืฉื™ื˜ืช ื ื™ืงื•ื“ Child-Pugh. ืงืฉื” ืœืื‘ื—ืŸ ืก"ื› ื‘ืฉืœื‘ื™ื ืžื•ืงื“ืžื™ื ืžืื•ื“ ื›ื™ ื ื“ืจืฉ ืฆื™ืจื•ืฃ ืฉืœ ื ื’ืข ื™ื—ื™ื“, ืืœโ€“ืชืกืžื™ื ื™, ืฉืงื•ื˜ืจื• ืงื˜ืŸ ืžโ€“2 ืก"ืž, ื‘ืœื™ ื’ืจื•ืจื•ืช. ื ื’ืขื™ื ืงื˜ื ื™ื ืžืกื•ื’ ื–ื” ืืคืฉืจ ืœื›ืจื•ืช ื‘ื”ืœื™ืš ื›ื™ืจื•ืจื’ื™, ื•ืฉื™ืขื•ืจ ื”ื”ื™ืฉืจื“ื•ืช ื”ื›ืœืœื™ ื‘ืžืงืจื™ื ืืœื• ืขืžื“ ืขืœ 90%. ื”ืงืจื™ื˜ืจื™ื•ื ื™ื ืฉืœ ืžื™ืœืืŸ ืžืืคืฉืจื™ื ืœืชื›ื ืŸ ืืช ืฆื•ืจืช ื”ื˜ื™ืคื•ืœ ื•ืœื‘ื—ื•ืจ ืืช ื”ื—ื•ืœื™ื ื”ืžืชืื™ืžื™ื ืœื”ืœื™ืš ื›ื™ืจื•ืจื’ื™ ืื• ืœื”ืฉืชืœื”, ื‘ื”ืชืื ืœืžืกืคืจ ื”ื ื’ืขื™ื ื•ืœื’ื•ื“ืœื. ืขื‘ื•ืจ ื—ื•ืœื™ ืก"ื› ื‘ืฉืœื‘ ืžื•ืงื“ื ื•ืชืคืงื•ื“ ื›ื‘ื“ื™ ืฉืžื•ืจ )Child-Pugh ืฉืœ A ืื• B( ืฉื™ืฉ ืœื”ื ื ื’ืข ืื—ื“ ื‘ืงื•ื˜ืจ ืฉืœ ืขื“ 5 ืก"ืž ืื• ืขื“ ืฉืœื•ืฉื” ื ื’ืขื™ื ืฉื”ืงื•ื˜ืจ ื”ืžืจื‘ื™ ืฉืœื”ื 3 ืก"ืž, ื˜ื™ืคื•ืœ ื”ื‘ื—ื™ืจื” ื ืงื‘ืข ืขืœ ืคื™ ืชืคืงื•ื“ ื”ื›ื‘ื“, ืžื™ื“ืช ื™ืชืจ ืœื—ืฅ ืคื•ืจื˜ืœื™ ื•ืžืฆื‘ื• ื”ื›ืœืœื™ ืฉืœ ื”ื—ื•ืœื” )ืœืจื‘ื•ืช ื‘ื—ื™ื ืช ืงื™ื•ืžืŸ ืฉืœ ืžื—ืœื•ืช ื’ื•ืคื ื™ื•ืช ืื—ืจื•ืช(. ื›ืจื™ืชื” ื›ื™ืจื•ืจื’ื™ืช ืžื•ืฆืขืช ืœื—ื•ืœื™ื ืœืœื ื™ืชืจ ืœื—ืฅ ืคื•ืจื˜ืœื™ ืฉื ืžืฆื ืืฆืœื ื ื’ืข ืื—ื“. ืœื—ื™ืœื•ืคื™ืŸ, ื”ื˜ื™ืคื•ืœ ื”ืžื•ืขื“ืฃ ื‘ืžืงืจื™ื ืืœื• ื”ื•ื ื”ืฉืชืœืช ื›ื‘ื“. ืฉื™ืขื•ืจ ื”ื”ื™ืฉืจื“ื•ืช ืขื“ 5 ืฉื ื™ื ื‘ื”ืœื™ืš ื–ื” ืขื•ืžื“ ืขืœ 75%. ืื ื”ืฉืชืœื” ืื™ื ื” ื–ืžื™ื ื”, ืื‘ืœืฆื™ื” ืžืงื•ืžื™ืช ื ื—ืฉื‘ืช ืœื˜ื™ืคื•ืœ ื”ื‘ื—ื™ืจื”. ื—ื•ืœื™ ืฉื—ืžืช ืžืคื•ืฆื”, ืœืœื ืชืกืžื™ื ื™ ืก"ื› ื•ืœืœื ืคืœื™ืฉื” ืœื›ืœื™ ื“ื, ืืš ืขื ืก"ื› ื’ื“ื•ืœ ืื• ืจื‘ ืžื•ืงื“ื™, ื ื—ืฉื‘ื™ื ืœื—ื•ืœื™ื ื‘ืฉืœื‘ ื‘ื™ื ื•ื ื™. ืขื‘ื•ืจ ื—ื•ืœื™ื ืืœื•, ื›ืžื•ืืžื‘ื•ืœื–ืฆื™ื” ื‘ื’ื™ืฉื” ืขื•ืจืงื™ืช )TACE( ืžืฉืคืจืช ืืช ืฉื™ืขื•ืจ ื”ื”ื™ืฉืจื“ื•ืช ืœืžืฉืš ืฉื ืชื™ื™ื ื‘โ€“25% ื‘ื”ืฉื•ื•ืื” ืœื˜ื™ืคื•ืœ ืฉืžืจื ื™. ืก"ื› ื”ืžืœื•ื•ื” ื‘ืชืกืžื™ื ื™ื ืงืœื™ื ื•ืคืœื™ืฉื” ืœื›ืœื™ ื“ื ืื• ื”ืชืคืฉื˜ื•ืช ื—ื•ืฅ ื›ื‘ื“ื™ืช ืžื•ื’ื“ืจ ื›ืžื—ืœื” ื‘ืฉืœื‘ ืžืชืงื“ื ื•ื˜ื™ืคื•ืœ ืจื“ื™ืงืœื™ ืื™ื ื• ืžืชืื™ื ื‘ืžืงืจื™ื ืืœื•. ื”โ€“TACE ื”ื•ื‘ื™ืœื” ืœืฉื™ืคื•ืจ ื‘ื”ื™ืฉืจื“ื•ืช TACEโ€“ื‘ืžืงืจื™ื ื ื‘ื—ืจื™ื, ื•ื˜ื™ืคื•ืœ ื”ื‘ื—ื™ืจื” ื‘ื—ื•ืœื™ื ืฉืื™ื ื ืžืชืื™ืžื™ื ืœื”ื•ื ืกื•ืจืคืื ื™ื‘. ืืฆืœ ื—ื•ืœื™ื ื‘ืžื—ืœื” ืกื•ืคื ื™ืช ื ืจืื™ื ื‘ื“"ื› ืชืกืžื™ื ื™ ืก"ื› ืขื“ ืื™โ€“ืกืคื™ืงืช ื›ื‘ื“, ืžืขื•ืจื‘ื•ืช ื›ืœื™ ื“ื ืื• ื”ืชืคืฉื˜ื•ืช ื—ื•ืฅ ื›ื‘ื“ื™ืช. ืฉื™ืขื•ืจ ื”ื”ื™ืฉืจื“ื•ืช ืœืฉื ื” ื‘ืงืจื‘ ื—ื•ืœื™ื ืกื•ืคื ื™ื™ื ืืœื• ื ืžื•ืš ืžโ€“10%, ื•ื”ื ืœื ื ื”ื ื™ื

ืžืžื’ื•ื•ืŸ ื”ื˜ื™ืคื•ืœื™ื ื”ื "ืœ.ื”ืฉืชืœืช ื›ื‘ื“ ืžืชื•ืจื ืžืช ื”ื™ื ื˜ื™ืคื•ืœ ื‘ื—ื™ืจื” ืœื—ื•ืœื™ ืก"ื› ื•ืฉื—ืžืช ื ื‘ื—ืจื™ื, ื•ื›ืจื•ื›ื” ื‘ืกื™ื›ื•ืŸ ื ืžื•ืš ืœื”ื™ืฉื ื•ืช ื”ื’ื™ื“ื•ืœ. ืœื—ื•ืœื™ ืก"ื› ื”ืขื•ื ื™ื ืขืœ ื”ืงืจื™ื˜ืจื™ื•ื ื™ื ืฉืœ ืžื™ืœืืŸ ืœื”ืฉืชืœื”, ืฆืคื•ื™ ืฉื™ืขื•ืจ ื”ื™ืฉืจื“ื•ืช ืฉืœ 85% ืœืืจื‘ืข ืฉื ื™ื ืื—ืจื™ ื”ืฉืชืœื” ื•ืกื™ื›ื•ื™ ืฉืœ 92% ืœืฉืจื•ื“ ื‘ืœื™ ื—ื–ืจืช ื”ื’ื™ื“ื•ืœ. ื”ื’ื™ืฉื” ืœืคื™ ื”ืงืจื™ื˜ืจื™ื•ื ื™ื ืฉืœ ืžื™ืœืืŸ ืื•ืžืชื” ื‘ืืจืฆื•ืช ื”ื‘ืจื™ืช, ื•ืื•ืžืฆื” ืขืœ ื™ื“ื™ ื”โ€“United Network for Organ Sharingื )UNOS(. ืžื“ื“ื™ ื”ื”ืขื“ืคื” Model for End- ืœื”ืฉืชืœื” ื‘ืืจืฆื•ืช ื”ื‘ืจื™ืช ืžืชื‘ืกืกื™ื ืขืœ ืฉื™ื˜ืชStage Liver Diseaseื )MELD(, ื•ืœืคื™ื” ื™ืฉ ืœื—ืฉื‘ ืืช ื”ืจืžื•ืช ื‘ืกืจื•ื ืฉืœ ื‘ื™ืœื™ืจื•ื‘ื™ืŸ, ืฉืœ ืงืจื™ืื˜ื™ื ื™ืŸ ื•ืฉืœ INR ืœืฉื ื—ื™ื–ื•ื™ ื—ื•ืžืจืช ืžื—ืœืช ื”ื›ื‘ื“. ื‘ืจื, ืฉื™ื˜ื” ื–ื• ืื™ื ื” ื™ืขื™ืœื” ืืฆืœ ื—ื•ืœื™ื ื”ืกื•ื‘ืœื™ื ื’ื ืžืก"ื›. ืขืœ ื›ืŸ ื—ื•ืœื™ MELD ื‘ืฉื ืช ืก"ื› ืžืงื‘ืœื™ื ืชื•ืกืคื•ืช ื ื™ืงื•ื“. ืžืื– ืื™ืžื•ืฅ ืฉื™ื˜ืช ื ื™ืงื•ื“ 2001, ืžืกืคืจื ืฉืœ ื—ื•ืœื™ ืก"ื› ืฉืขื•ื‘ืจื™ื ื”ืฉืชืœืช ื›ื‘ื“ ื”ื•ืœืš ื•ืขื•ืœื”. ื‘ืžืงื‘ื™ืœ, ืคื•ืชื—ื• ื‘ืื•ื ื™ื‘ืจืกื™ื˜ืช ืกืŸึพืคืจื ืกื™ืกืงื• )UCSF( ืžื“ื“ื™ื ืœื”ืจื—ื‘ืช ืžืื’ืจ ื”ืžื•ืขืžื“ื™ื ื—ื•ืœื™ ืก"ื› ืœื”ืฉืชืœื” ืžืขื‘ืจ ืœืงืจื™ื˜ืจื™ื•ื ื™ื ืฉืœ ืžื™ืœืืŸ. ืื ื”ื—ื•ืœื” ืื™ื ื• ืžืชืื™ื ืœืฉืชื™ ื”ืฉื™ื˜ื•ืช )MILAN ื•ื’ื UCSF(, ื”ื•ื ืขื•ื‘ืจ radio ืื• ืื‘ืœืฆื™ื” ืขืœโ€“ื™ื“ื™ TACE ื‘ื—ืœืง ืžื”ืžืจื›ื–ื™ื ื‘ืืจืฆื•ืช ื”ื‘ืจื™ืช ื˜ื™ืคื•ืœื™)Down staging( ื›ื“ื™ ืœืฆืžืฆื ืืช ื ืคื— ื”ืžื—ืœื” frequency ablation ื–ื• ืžืฉืชื ื” ื•ืœืืคืฉืจ ืœื• ืœื”ืชืื™ื ืœืงืจื™ื˜ืจื™ื•ื ื™ื ื”ื "ืœ. ื”ืฆืœื—ืช ื’ื™ืฉื”

ื‘ืžืจื›ื–ื™ื ืฉื•ื ื™ื. )RF( radio frequency ablation ื”ืฉื™ืžื•ืฉ ื‘ื˜ื™ืคื•ืœื™ ืื‘ืœืฆื™ื” ืžืงื•ืžื™ื™ืื”ืชื’ื‘ืจ ืขื ื”ื–ืžืŸ ื•ื”ื ื”ืคื›ื• ืœืฉื›ื™ื—ื™ื. ื–ื• ื”ืฉื™ื˜ื” ื”ืžื•ืขื“ืคืช ืœื˜ื™ืคื•ืœ ื‘ืกืจื˜ืŸ ื›ื‘ื“ ื‘ืฉืœื‘ ืžื•ืงื“ื, ื›ืืฉืจ ื”ืฉืชืœื” ืื• ื›ืจื™ืชื” ืื™ื ื ื–ืžื™ื ื™ื. ืžื—ืงืจื™ื ืฉืขืฉื• ืจื ื“ื•ืžื™ื–ืฆื™ื” ื‘ืื™ื›ื•ืช ื˜ื•ื‘ื”, ื”ืจืื• ืฉื˜ื™ืคื•ืœ RF ื™ืขื™ืœ ื™ื•ืชืจ ืžื”ืฉื™ื˜ื” ื”ื™ืฉื ื” ืฉืœ ื”ื–ืจืงืช ืืชื ื•ืœ ื‘ื’ื•ืฉื™ื ืฉืงื•ื˜ืจื 3-2 ืก"ืž, ื•ืžื•ื‘ื™ืœ

ืœืฉื™ืขื•ืจ ื ืžื•ืš ื™ื•ืชืจ ืฉืœ ื—ื–ืจื” ืžืงื•ืžื™ืช ื•ืœืขืœื™ื™ื” ื‘ืฉื™ืขื•ืจ ื”ื”ื™ืฉืจื“ื•ืช ืœืœื ื’ื™ื“ื•ืœ ]2[. ืชื•ืฆืื•ืช ืงืฆืจื•ืช ื˜ื•ื•ื— ื‘ื˜ื™ืคื•ืœ ื–ื” ื”ืจืื• ืฉื™ืขื•ืจื™ ื”ื™ืฉืจื“ื•ืช ืฉืœ 100% ื•โ€“98% ื‘ืžืขืงื‘ ืฉืœ ืฉื ื” ื•ืฉื ืชื™ื™ื, ื‘ื”ืชืืžื”. ืžืขืงื‘ ืืจื•ืš ื˜ื•ื•ื— ื”ืจืื” ื”ื™ืฉืจื“ื•ืช ื‘ืฉื™ืขื•ืจ ืฉืœ 70% ื‘ืžืขืงื‘ ืขื“ 5 ืฉื ื™ื. ืชื•ืฆืื•ืช ืฉื ื™ ืžื—ืงืจื™ื ืฉื”ืฉื•ื• ื‘ืฆื•ืจื” ืืงืจืื™ืช ื‘ื™ืŸ RF ืœื‘ื™ืŸ ื›ืจื™ืชื” ื›ื™ืจื•ืจื’ื™ืช ื”ืจืื• ืชื•ืฆืื•ืช ื“ื•ืžื•ืช ืžื‘ื—ื™ื ืช ื”ื™ืฉืจื“ื•ืช ืœืœื ื’ื™ื“ื•ืœ, ืืš ื›ืฆืคื•ื™ RF ื”ื™ื” ื›ืจื•ืš

ื‘ืฉื™ืขื•ืจ ืžื•ืคื—ืช ืฉืœ ืกื™ื‘ื•ื›ื™ื ื•ืฉืœ ืืฉืคื•ื–ื™ื.ื›ืžื•ืืžื‘ื•ืœื–ืฆื™ื” ืชื•ืš ืขื•ืจืงื™ืช ื•ืจื“ื™ื•ืืžื‘ื•ืœื™ื–ืฆื™ื” )TACE( ื”ื•ื‘ื™ืœื• ืœืฉื™ืคื•ืจ ื‘ื”ื™ืฉืจื“ื•ืช ื‘ืงืจื‘ ื—ื•ืœื™ื ืฉืชืคืงื•ื“ ื–ื” ื›ื‘ื“ ืืฆืœื ืฉืžื•ืจ, ื‘ืคืจื˜ ื—ื•ืœื™ ื’ืจื•ืจื•ืช ื—ื•ืฅ ื›ื‘ื“ื™ื•ืช, ืคืœื™ืฉื” ืœื›ืœื™ ื“ื Child-A ืฉืื™ืŸ ืœื”ื ืฉื—ืžืช ืื• ืชืกืžื™ืŸ ืก"ื› ื‘ื•ืœื˜. ื‘ืžื˜ื”โ€“ืื ืœื™ื–ื” ืฉืœ ืกื“ืจื•ืช ืžื‘ื•ืงืจื•ืช ืืงืจืื™ื•ืช ืฉื”ืขืจื™ื›ื• ืืช ื”ืฉื™ืžื•ืฉ ื‘ืืžื‘ื•ืœื™ื–ืฆื™ื” ืขื•ืจืงื™ืช, ื‘ื›ืžื•ืืžื‘ื•ืœื–ืฆื™ื”, ืื• ื‘ืฉืชื™ ื”ืฉื™ื˜ื•ืช ื›ื˜ื™ืคื•ืœ ืคืœื™ืื˜ื™ื‘ื™ ืœื—ื•ืœื™ ืก"ื›, ื ืจืื” ืฉื™ืคื•ืจ ื‘ืฉื™ืขื•ืจื™ ื”ื™ืฉืจื“ื•ืช ืฉืœ ืฉื ืชื™ื™ื ื‘ื”ืฉื•ื•ืื” ืœื˜ื™ืคื•ืœ ืฉืžืจื ื™. ืœื ื‘ืจื•ืจื” ืชืจื•ืžืช TACE ืœื”ืงื˜ื ืช ื ืคื— ื”ื’ื™ื“ื•ืœ ืœืคื ื™ ื”ืฉืชืœื”. ืชืกืžื•ื ืช ืื™ืกื›ืžื™ื” ื›ื‘ื“ื™ืช ืœืื—ืจ TACE ื ืจืืชื” ืืฆืœ ืžื—ืฆื™ืช ืžื”ืžื˜ื•ืคืœื™ื. ื‘ืžื—ืงืจ ืขื“ื›ื ื™ ืžื‘ื•ืงืจ ื ืžืฆื ื›ื™ ื”ืฉื™ืžื•ืฉ ื‘ื—ืœืงื™ืงื™ื ื”ืžืฉื—ืจืจื™ื ืชืจื•ืคื” ื‘ืฆื•ืจื” ืžื‘ื•ืงืจืช ื‘ืžื”ืœืš TACE ื”ื™ื” ื›ืจื•ืš ื‘ื™ืจื™ื“ื” ื‘ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื‘ื›ื‘ื“ ื•ื‘ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื”ืžืขืจื›ืชื™ื•ืช, ื•ื‘ืขืœื™ื™ื” ื‘ืชื’ื•ื‘ื” ื”ืžืงื•ืžื™ืช ืฉืœ ื”ื’ื™ื“ื•ืœ. ืจื“ื™ื•ืืžื‘ื•ืœื™ื–ืฆื™ื” ืขื ืžื™ืงืจื•ืกืคืจื•ืช ืฉืœ yttrium-90 ืœื˜ื™ืคื•ืœ ื‘ื—ื•ืœื™ ืฉื—ืžืช Child-A ื ืžืฆืืช

ืขื“ื™ื™ืŸ ื‘ื‘ื“ื™ืงื”. ืขื“ ื›ื” ืื™ืŸ ื˜ื™ืคื•ืœ ื›ื™ืžื•ืชืจืคื™ ืกื™ืกื˜ืžื™ ืฉื”ื•ื›ื— ื›ื™ืขื™ืœ. ืกื•ืจืืคื ื™ื‘ ื”ื•ื ืžื•ืœืงื•ืœื” ืงื˜ื ื”, ืžืขื›ื‘ ืจื‘ ืงื™ื ื–ื•ืช, ืฉื ื™ืชืŸ ืคื•ืžื™ืช ืœื”ื•ืจื“ืช ื—ืœื•ืงืช ื”ืื—ืจื•ื ื”, ื‘ืชืงื•ืคื” ืฉื ืขืจื›ื• ืืงืจืื™ืช ืžื‘ื•ืงืจื™ื ืžื—ืงืจื™ื ืชืื™ื. ื”ืฆื‘ื™ืขื• ืขืœ ืขืœื™ื™ื” ืฉืœ ืขื“ 37% ื‘ื”ื™ืฉืจื“ื•ืช ื”ื›ืœืœื™ืช ื‘ื”ืฉื•ื•ืื” ืœืคืœืฆื‘ื• ื‘ืงืจื‘ ื—ื•ืœื™ ืก"ื› ื•ืฉื—ืžืช ืžืคื•ืฆื” ]2[. ืคืจื™ื—ื” ื‘ื™ื“ื™ื™ื ื•ื‘ื›ืคื•ืช ื”ืจื’ืœื™ื™ื, ืฉืœืฉื•ืœ ื•ื—ื•ืœืฉื” ื”ื ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื”ืฉื›ื™ื—ื•ืช. ื›ืžื” ืขื‘ื•ื“ื•ืช ื”ืขืจื™ื›ื• ืืช ื”ื™ืขื™ืœื•ืช ืฉืœ ืกื•ืจืืคื ื™ื‘ ื‘ืฉื™ืœื•ื‘ ืขื TACE. ื™ืฉื ืŸ ื’ื ืชืจื•ืคื•ืช ื—ื“ื™ืฉื•ืช bevacizumab ื•ื ื•ื’ื“ื ื™ื ืžื•ื ื•ืงืœื•ื ืืœื™ื™ื ื›ื’ื•ืŸ erlotinibโ€“ื• brivanib ื›ืžื•

ื•โ€“cetuximab ืืš ืขื“ื™ื™ืŸ ืœืœื ืชื•ืฆืื•ืช ืžืงื“ื™ืžื•ืช.

ืœืกื™ื›ื•ื: ืจืง 29% ืžื—ื•ืœื™ ืก"ื› ืžืื•ื‘ื—ื ื™ื ื–ื›ื• ืœื‘ื“ื™ืงื•ืช ืกืจื™ืงื” ื‘ืฉืœื•ืฉ ื”ืฉื ื™ื ืฉืœืคื ื™ ืื‘ื—ื•ืŸ ื”ืžื—ืœื”. ืจืง 13% ืžื—ื•ืœื™ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืžืกื•ื’ C ื•ืฉื—ืžืช ืขื•ื‘ืจื™ื ื‘ื“ื™ืงื•ืช ืกืจื™ืงื”. ืœืคื™ื›ืš ื”ื ื™ืฆื•ืœ ืฉืœ ื”ืฉืชืœื•ืช ื›ื‘ื“, ืฉืœ ื›ืจื™ืชื” ื›ื™ืจื•ืจื’ื™ืช ื•ืฉืœ TACE ื”ื•ื ื ืžื•ืš. ื™ืฉ ืœื ืงื•ื˜ ืฆืขื“ื™ื ื ื•ืกืคื™ื ืœืฉื™ืคื•ืจ ืชื•ืฆืื•ืช ื”ืžื—ืœื”, ื›ื•ืœืœ ื”ืขืœืืช ืžืกืคืจ ื”ื—ื•ืœื™ื ื”ืžืื•ื‘ื—ื ื™ื ื‘ืฉืœื‘ื™ื ืžื•ืงื“ืžื™ื. ืืคืฉืจ ืœืขืฉื•ืช ื–ืืช ืขืœโ€“ื™ื“ื™ ื”ื˜ืžืขืช ื‘ื“ื™ืงื•ืช ืกืจื™ืงื”, ื˜ื™ืคื•ืœ ืžื•ืชืื ืœืžื—ืœื” ื‘ืกื™ืกื™ืช, ืฉื™ืžื•ืฉ ื‘ืžืขืจื›ื•ืช ืœื”ืขืจื›ืช ืฉืœื‘ ื”ืžื—ืœื”

ื•ื’ื™ืฉื” ืฉืœ ื”ืžื˜ื•ืคืœ ืœืฆื•ื•ืช ืžื˜ืคืœ ืจื‘โ€“ืชื—ื•ืžื™.

ื‘ื™ื‘ืœื™ื•ื’ืจืคื™ื”1. World Health Organization, International Agency for Research on

Cancer. GLOBOCAN 2008. (http://globocan.iarc.fr).

2. El-Serag HB. Hepatocellular Carcinoma. N Engl J Med 2011; 365:1118-1127

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ืœืขืœื•ืช ืขื“ ืคื™ 70. ืชื’ื•ื‘ื” ื‘ื™ืŸโ€“ืชืจื•ืคืชื™ืช ืขืœื•ืœื” ืœื”ื™ื•ื•ืฆืจ ื’ื ื‘ื ื˜ื™ืœืช ื‘ื”ื™ืคืจืœื™ืคื™ื“ืžื™ื” ,)efavirenz( HIVโ€“ื‘ ืœื˜ื™ืคื•ืœ ืชืจื•ืคื•ืช ื”ืžืฉืžืฉื•ืช )atorvastatin( ืื• ื‘ื™ืชืจ ืœื—ืฅ ื“ื )amlodipine(. ื‘ืฉืœื‘ ื–ื” ื—ืกืจ ืžื™ื“ืข ืžืžื™ื“ืข ืื•ืœื ืชื›ื•ืฃ, ื™ื•ืžื™ ื‘ืฉื™ืžื•ืฉ ื”ื ืžืฆืื•ืช ืจื‘ื•ืช ืชืจื•ืคื•ืช ืœื’ื‘ื™ ืฉื”ืฆื˜ื‘ืจ ืขื“ ื›ื” ื‘ืจื•ืจ ืฉื™ืฉ ืœื ืงื•ื˜ ืžืฉื ื” ื–ื”ื™ืจื•ืช ื•ืœื”ืชื—ืฉื‘ ื‘ืชื’ื•ื‘ื•ืช ืืœื” ื•ืื—ืจื•ืช ื‘ื˜ื™ืคื•ืœ ื‘โ€“DAAs ื‘ืžื™ื•ื—ื“ ื‘ืขืช ื˜ื™ืคื•ืœ ื‘ื—ื•ืœื™ื ืžื•ืฉืชืœื™ ื›ื‘ื“

ื•ื—ื•ืœื™ HIV, ืฉื”ื˜ื™ืคื•ืœ ื‘โ€“DAAs ื™ืขืœื” ืืฆืœื ืขืœ ื”ืคืจืง ื‘ืขืชื™ื“ ื”ืงืจื•ื‘.

ืžื” ืฆืคื•ื™ ื‘ืขืชื™ื“? ืžื”ื—ื•ืœื™ื ื‘ื—ืœืง ืœื˜ืคืœ ืžืงื•ื ื‘ื”ื—ืœื˜ ื™ืฉ ื–ื” ืฉื‘ืฉืœื‘ ืœืฆื™ื™ืŸ ืจืื•ื™ ื˜ื‘ืœื” ืœื›ืŸ. ืงื•ื“ื ืฉื”ื•ื–ื›ืจ ื›ืคื™ ,DA As ื”โ€“ ืฉื™ืœื•ื‘ ืœืœื SOC ื‘โ€“ DA Asโ€“ื” ืฉืœ ื”ืฉื•ื ื•ืช ื”ืงื‘ื•ืฆื•ืช ื‘ื™ืŸ ื”ืฉื•ื ื™ ืืช ืžืจืื” 2 ืžืกืคืจ ื•ืœื™ืขื™ืœื•ืช ื”ืขืžื™ื“ื•ืช ืœืคืจื•ืคื™ืœ ื”ืื ื˜ื™โ€“ื•ื™ืจืืœื™ืช, ืœื™ืขื™ืœื•ืช ื‘ื”ืชื™ื™ื—ืก ื”ื˜ื™ืคื•ืœ ื”ืงืจื•ื‘ื•ืช ื‘ืฉื ื™ื ื”ื ืจืื”, ื›ื›ืœ ืฉื•ื ื™ื. ื’ื ื•ื˜ื™ืคื™ื ื ื’ื“ ื‘โ€“pegIFNฮฑ ื•ื‘ืจื™ื‘ื•ื™ืจื™ืŸ ื™ื”ื™ื” ื”ื‘ืกื™ืก ืœื˜ื™ืคื•ืœ ื‘ืฉื™ืœื•ื‘ ืขื DAAs, ื•ื–ืืช ื›ื“ื™ ืœืžื ื•ืข ืขืžื™ื“ื•ืช ื•ื”ื™ืฉื ื•ืช ืฉืœ ื”ื–ื™ื”ื•ื ื”ื ื’ื™ืคื™. ื‘"ื’ืœ" ื”ื‘ื ืฉืœ ื”ืชืจื•ืคื•ืช, ื‘ื›ืœืœ ื–ื” ื”"ื“ื•ืจ ื”ืฉื ื™" ืฉืœ ื”โ€“DAAs, ื”ืชืจื•ืคื•ืช ืชื”ื™ื™ื ื” ื ื•ื—ื•ืช ื™ื•ืชืจ ืœืฉื™ืžื•ืฉ )ื˜ื‘ืœื™ื” ืื—ืช ืื• ืฉืชื™ื™ื ื‘ื™ื•ื(, ืกื‘ื™ืœื•ืช ื™ื•ืชืจ ืžื‘ื—ื™ื ืช ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™, ื”ืกื™ื›ื•ื™ ืœื”ืชืคืชื—ื•ืช ื–ื ื™ื ืขืžื™ื“ื™ื ื™ื”ื™ื” ื ืžื•ืš ื™ื•ืชืจ ื•ื˜ื•ื•ื— ื”ืคืขื•ืœื” pegIFN ื ื’ื“ ื’ื ื•ื˜ื™ืคื™ื ื•ื™ืจืืœื™ื™ื ืฉื•ื ื™ื ื™ื”ื™ื” ืจื—ื‘ ื™ื•ืชืจ. ื”ืฉื™ืœื•ื‘ ืฉืœ nucleosideโ€“( ืขื ืžืขื›ื‘ื™ ืคืจื•ื˜ื™ืื–ื”, ืžืขื›ื‘ื™ ืคื•ืœื™ืžืจืื– )ื‘ืขื™ืงืจ ื”RBVยฑ(inhibitors( ืื• ืžืขื›ื‘ื™ NS5A ื ืจืื” ืžื‘ื˜ื™ื— ื‘ื—ืœืง ืžื”ืžื—ืงืจื™ื ืฉื‘ื•ืฆืขื• ืขื“ ื›ื”. ืฉื™ืœื•ื‘ื™ื ืฉืœ pegIFN ืขื ื›ืžื” ืชืจื•ืคื•ืช ืžืงื‘ื•ืฆื•ืช ืฉื•ื ื•ืช ืœืœื NS5A ืขืžื™ื“ื•ืช ืฆื•ืœื‘ืช )ืžืขื›ื‘ื™ ืคืจื•ื˜ื™ืื–ื” + ืžืขื›ื‘ื™ ืคื•ืœื™ืžืจืื–ื” ืื• ืžืขื›ื‘ื™ )ยฑRBV(( ื ืžืฆืื™ื ื›ืขืช ื‘ืฉืœื‘ ืฉืœ ื‘ื“ื™ืงื”, ื•ืชื•ืฆืื•ืช ื”ื‘ื™ื ื™ื™ื ื‘ื”ื—ืœื˜

ืžืขื•ื“ื“ื•ืช. ื›ืžื” ืžื—ืงืจื™ื ื‘ื•ื“ืงื™ื ืืช ื”ืืคืฉืจื•ืช ืฉืœ ืฉื™ืœื•ื‘ื™ื ืฉื•ื ื™ื ืื™ื ื˜ืจืคืจื•ืŸ" โ€œื ื˜ื•ืœ ื‘ื˜ื™ืคื•ืœ ืฉื•ื ื•ืช ืคื•ืžื™ื•ืช ืžืงื‘ื•ืฆื•ืช ื‘ื™ืŸ ืชืจื•ืคื•ืช ื”ืžื‘ื˜ื™ื— ืกื‘ื™ืœื•ืช ื˜ื•ื‘ื” ื™ื•ืชืจ. ื˜ื™ืคื•ืœื™ื ื ื˜ื•ืœื™ ืื™ื ื˜ืจืคืจื•ืŸ ื•ืจื™ื‘ื•ื™ืจื™ืŸ ื™ื•ืขื™ืœื• ,SOCโ€“ืฉืื™ื ื ืจื’ื™ืฉื™ื ื›ืœืœ ืœ ,null responders ื‘ืขื™ืงืจ ืœื—ื•ืœื™ื ืฉื”ื ,SOCโ€“ืฉื”ืกื‘ื™ืœื•ืช ืฉืœื”ื ืœื˜ื™ืคื•ืœ ื ืžื•ื›ื” ืื• ืฉื™ืฉ ืืฆืœื ื”ืชื•ื•ื™ื•ืช ื ื’ื“ ืœื•ืœื—ื•ืœื™ ืฉื—ืžืช ืœื ืžืื•ื–ื ืช )decompensated cirrhosis(. ื™ืฉ ืœื–ื›ื•ืจ ืฉืขื“ื™ื™ืŸ ืื™ืŸ ืžื™ื“ืข ืžืกืคืง ืขืœ ื”ืฉื™ืžื•ืฉ ื‘ืชืจื•ืคื•ืช ืืœื• ื‘ืื•ื›ืœื•ืกื™ื•ืช ืฉื•ื ื•ืช HIV-coinfection. ืขื“ ื›ื” ื”ื•ืฉื’ื• ืฉืœ ื—ื•ืœื™ื ื›ืžื• ืžื•ืฉืชืœื™ ื›ื‘ื“ ื•ื—ื•ืœื™ ืชื•ืฆืื•ืช ื‘ื™ื ื™ื™ื ืžืจืฉื™ืžื•ืช ื‘ื—ืœืง ืžื”ืฉื™ืœื•ื‘ื™ื, ืื•ืœื ื ืฆื˜ืจืš ืœื”ืžืชื™ืŸ ืขื•ื“ ื›โ€“5 ืฉื ื™ื ืขื“ ืœืงื‘ื™ืขืช โ€œืฉื™ืœื•ื‘ื™ื ืžื ืฆื—ื™ื". ื™ื—ื“ ืขื ื–ืืช ื”ืื•ืคืง

ื”ื˜ื™ืคื•ืœื™ ื ืจืื” ื•ืจื•ื“.

ื‘ื™ื‘ืœื™ื•ื’ืจืคื™ื”1. McHutchinson JG, Manns MP, Muir AJ, et al. Telaprevir for

previously treated chronic HCV infection. PROVE 3 Study Team. N Engl J Med 2010, 362:1292-303.

2. Jacobson I, McHutchinson JG, Dusheiko G, et al. ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011, 364(25):2405-16.

3. Zeuzem S, Andreone P, Pol S, et al. REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med 2011, 364(25):2417-28.

4. Bacon B, Gordon S, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection (RESPOND-2). N Engl J Med 2011, 364:1207-17.

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”

ื”ืชืžื•ื“ื“ื•ืช ืขื ื”ืชืคืชื—ื•ืช ืขืžื™ื“ื•ืช ืœืžืขื›ื‘ื™ ืคืจื•ื˜ื™ืื–ื” ืžืกืชื‘ืจ ืฉืืคืฉืจ ืœื’ืœื•ืช ื–ื ื™ื ืขืžื™ื“ื™ื ืœืžืขื›ื‘ื™ ืคืจื•ื˜ื™ืื–ื” ื‘ืฉื™ืขื•ืจ ื ืžื•ืš )<1%( ืืฆืœ ื—ื•ืœื™ื โ€œื ืื™ื‘ื™ื™ื" ืขื•ื“ ืœืคื ื™ ื”ืชื—ืœืช ื”ื˜ื™ืคื•ืœ ื•ืืฆืœ 0.3%-1.8% ืžื”ื—ื•ืœื™ื ื”ืžื ื•ืกื™ื ืœืคื ื™ ื˜ื™ืคื•ืœ. ื‘ืงืจื‘ ื—ื•ืœื™ื ื”ืžื’ื™ื‘ื™ื ืœืื™ื ื˜ืจืคืจื•ืŸ, ืฉื™ืขื•ืจ ื”ืขืžื™ื“ื•ืช ืœโ€“DAAs ืงื˜ืŸ ื‘ืื•ืคืŸ ืžืฉืžืขื•ืชื™, ื›ืคื™ ืฉื ืฆืคื” ื‘ืžื—ืงืจ ืฉื”ื’ื™ื‘ื• ืžื”ื—ื•ืœื™ื 4% ืืฆืœ ื ืฆืคืชื” BOCโ€“ืœ ืขืžื™ื“ื•ืช :SPRINT-2ืœืื™ื ื˜ืจืคืจื•ืŸ )ื™ืจื™ื“ื” ืฉืœ โ‰ค 1log10 ืชื•ืš ื›ื“ื™ ืฉืœื‘ ื”โ€“lead-in( ื‘ืขื•ื“ ืฉื™ืขื•ืจ ื”ืขืžื™ื“ื•ืช ืขืœื” ืœโ€“47% ื‘ืงืจื‘ ื—ื•ืœื™ื ืฉืœื ื”ื’ื™ื‘ื•. ื™ื—ื“ ืขื ื–ืืช, ื”ื–ื ื™ื

ื”ืขืžื™ื“ื™ื ืื™ื ื ื ื™ืชื ื™ื ืœื’ื™ืœื•ื™ ืœืื—ืจ ืชืงื•ืคืช ืžืขืงื‘ ืฉืœ ื›ืฉื ืชื™ื™ื )ื•ืืฃ ืคื—ื•ืช( ืžื”ืคืกืงืช ื”ื˜ื™ืคื•ืœ ื‘โ€“DAAs ืืฆืœ 88%-100% ืžื”ื—ื•ืœื™ื, ื›ืคื™ ืฉื”ื•ื“ื’ื ื‘ืžื—ืงืจ ื”โ€“EXTEND. ืœืคื™ื›ืš ื”ื—ืฉืฉ ืžื”ื•ืคืขืช ื–ื ื™ื ืขืžื™ื“ื™ื ืœื ืฆืจื™ืš ืœื”ื™ื•ืช ื›ื” ื’ื“ื•ืœ ื•"ืžืฉืชืง". ื”ืคืกืงืช ื”ื˜ื™ืคื•ืœ ื‘โ€“DAAs ื‘ืฉืœ ื‘ืขื™ื™ืช ืขืžื™ื“ื•ืช ืื™ื ื” ืคื•ื’ืžืช ื‘ืื•ืคืŸ ืžืฉืžืขื•ืชื™ ื‘ื™ื›ื•ืœืช ืœื”ื’ื™ื‘ ืœื˜ื™ืคื•ืœ ื—ื•ื–ืจ ื‘ืขืชื™ื“ ื‘ืžืขื›ื‘ื™ ืคืจื•ื˜ื™ืื–ื” ืื—ืจื™ื )ืืคื™ืœื• ืขื ืขืžื™ื“ื•ืช ืฆื•ืœื‘ืช( ื•ื‘ื•ื•ื“ืื™ ืฉืื™ื ื” ืคื•ื’ืขืช ื‘ื˜ื™ืคื•ืœ ื‘ืชืจื•ืคื•ืช ืžืงื‘ื•ืฆื•ืช ืื—ืจื•ืช ืœืœื ืขืžื™ื“ื•ืช ืฆื•ืœื‘ืช. ืœืžืจื•ืช ื–ืืช, ืขืœ ืžื ืช ืœืžื ื•ืข ื”ื•ืคืขืช ื–ื ื™ื ืขืžื™ื“ื™ื ืœืชืจื•ืคื•ืช ืจื‘ื•ืช ื•ืขืœ ืžื ืช ืœืžื–ืขืจ ืืช ื‘ืขื™ื™ืช ื”ืขืžื™ื“ื•ืช, ื™ืฉ ืœื”ื™ืฆืžื“ ื‘ืงืคื“ื ื•ืช ืจื‘ื” ืœื ืงื•ื“ื•ืช ื”ื–ืžืŸ

ืœื”ืคืกืงื” ืžื•ืงื“ืžืช ืฉืœ ื”ื˜ื™ืคื•ืœ, ืฉื–ื•ื”ื™ ืžื˜ืจืชื”.

ืžื•ืจื›ื‘ื•ืช ื”ื˜ื™ืคื•ืœ ื—ื“ืฉื•ืช ื–ืžืŸ ื ืงื•ื“ื•ืช ื ื•ืกืคื• ื”ืคืจื•ื˜ื™ืื–ื” ื‘ืžืขื›ื‘ื™ ื”ืžืฉื•ืœื‘ ื‘ื˜ื™ืคื•ืœ ืœื”ืขืจื›ื”, ื”ืŸ ื›ืืœื” ื”ืงืฉื•ืจื•ืช ืœโ€“"stopping rules" ื•ื”ืŸ ื›ืืœื” ื”ืงืฉื•ืจื•ืช lead-inโ€“ื ื•ืกืฃ ืœืืœื”, ืฉืœื‘ ื” .)RGT( ืœืงื‘ื™ืขืช ื˜ื™ืคื•ืœโ€“ืžื•ื ื—ื” ืชื’ื•ื‘ื”ื‘ื˜ื™ืคื•ืœ ื‘โ€“BOC ืžื•ืกื™ืฃ ืœืžื•ืจื›ื‘ื•ืช ืฉืœ ื”ื˜ื™ืคื•ืœ. ื”ื”ื™ื’ื™ื•ืŸ ื‘ืงื™ื•ื ืฉืœื‘ lead-in ื”ื•ื ืฉื™ืจื™ื“ืช ื”ืขื•ืžืก ื”ื ื’ื™ืคื™ ืœืคื ื™ ื”ืฉื™ืžื•ืฉ ื‘โ€“DAAs ืžืกื™ื™ืขืช ื•ืชื’ื•ื‘ื” ื•ื‘ื–ื™ื”ื•ื™ ืจื’ื™ืฉื•ืช ื–ื ื™ื ืขืžื™ื“ื™ื ื‘ื”ื•ืจื“ืช ืฉื™ืขื•ืจ ื”ื•ืคืขืชื ืฉืœ ืœืื™ื ื˜ืจืคืจื•ืŸ, ื•ืขื•ื–ืจืช ื‘ืงื‘ืœืช ื”ื—ืœื˜ื” ืžืชืื™ืžื” ืœื˜ื™ืคื•ืœ ืขืœ ืคื™ ื”ืชื’ื•ื‘ื” SVR ืœืื—ืจ 4 ืฉื‘ื•ืขื•ืช. ืืš ืœื ื›ืš ืคื ื™ ื”ื“ื‘ืจื™ื: ืืžื ื ืฉื™ืขื•ืจ ื”ืฉื’ืชื‘ืงืจื‘ ื—ื•ืœื™ื ืฉื”ื’ื™ื‘ื• ืœโ€“lead-in )ื™ืจื™ื“ืช HCV RNA ื‘โ€“1log10 ืื• ื™ื•ืชืจ( ื”ื™ื” ื›โ€“80% ืœืขื•ืžืช ื›โ€“30% ื‘ืงืจื‘ ื—ื•ืœื™ื ืฉืœื ื”ื’ื™ื‘ื•, ืืš ื”ืชื•ืฆืื” ืœื ืžื•ื‘ื™ืœื” ืœื”ื—ืœื˜ื” ื˜ื™ืคื•ืœื™ืช. ื”ื™ืขื™ืœื•ืช ื‘ื”ื•ืจื“ืช ืฉื™ืขื•ืจ ื”ื•ืคืขืชื” ืฉืœ ืขืžื™ื“ื•ืช ืื• ื‘ื”ืฉื’ืช SVR ืื™ื ื” ื‘ืจื•ืจื” ื•ืœื ื”ื•ื›ื—ื”. ื™ืชืจื•ืŸ ื”ืฉื™ืžื•ืฉ ื‘โ€“

,RVR ืงืฉื•ืจ ืœืืคืฉืจื•ืช ืฉืœ ืงื™ืฆื•ืจ ื”ื˜ื™ืคื•ืœ ืขื‘ื•ืจ ื—ื•ืœื™ื ืฉื”ืฉื™ื’ื• lead-inื–ื™ื”ื•ื™ ื—ื•ืœื™ื ืฉืื™ื ื ื–ืงื•ืงื™ื ืœื˜ื™ืคื•ืœ ื‘โ€“DAAs ื•ื–ื™ื”ื•ื™ ื—ื•ืœื™ื ืฉื”ื”ื™ืขื ื•ืช ืฉืœื”ื ืœื˜ื™ืคื•ืœ ื‘ื›ืœืœ ื™ืจื•ื“ื”, ื›ืš ืฉื”ื•ื ื™ื•ืคืกืง ื›ื‘ืจ ื‘ืžื”ืœืš 4 ื”ืฉื‘ื•ืขื•ืช ื”ืจืืฉื•ื ื™ื )<5%(. ื‘ืฉืœ ืžื•ืจื›ื‘ื•ืช ื”ื˜ื™ืคื•ืœ, ืœื ื™ื•ื›ืœ ื›ืœ ืจื•ืคื ืžืŸ ื”ืฉื•ืจื” ืœืงื—ืช ืขืœ ืขืฆืžื• ืืช ื ื™ื”ื•ืœ ื”ื˜ื™ืคื•ืœ ืœืœื ื”ื›ืฉืจื” ืžื•ืงื“ืžืช ื•ืœืœื ืžืขืจื›ืช ืชืžื™ื›ื” ื•ื™ื“ืข ื ืจื—ื‘ ื‘ื›ืœ ื”ื ื•ืฉืื™ื ื”ื›ืจื•ื›ื™ื ื‘ื ื™ื˜ื•ืจ ื•ื‘ื˜ื™ืคื•ืœ ื‘ืชื•ืคืขื•ืช

ื”ืœื•ื•ืื™.

ื˜ื™ืคื•ืœ ื‘ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ืžืฉืžืขื•ืชื™ื•ืช ืœื•ื•ืื™ ื‘ืชื•ืคืขื•ืช ื›ืจื•ืš BOC ื•ื‘โ€“ TPV ื‘โ€“ ื”ื˜ื™ืคื•ืœ ื”ืœื•ื•ืื™ ืชื•ืคืขื•ืช ื ื•ืกืฃ. ื•ื˜ื™ืคื•ืœ ืชื›ื•ืฃ ื ื™ื˜ื•ืจ ืขืจื ื•ืช, ื”ืžื—ื™ื™ื‘ื•ืช ืืฆืœ ื’ืจื“ ื”ืŸ TP V ื‘โ€“ ื‘ื˜ื™ืคื•ืœ ื‘ื™ื•ืชืจ ื•ื”ืฉื›ื™ื—ื•ืช ื”ื‘ื•ืœื˜ื•ืช

45%-50% ืžื”ืžื˜ื•ืคืœื™ื, ืชืคืจื—ืช ื‘ืขื•ืจ ืืฆืœ 35%-37%, ื‘ื—ื™ืœื” ืืฆืœ 40%-43% ื•ืื ืžื™ื” ืืฆืœ 37%-39% ืžื”ืžื˜ื•ืคืœื™ื. ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื”ืฉื›ื™ื—ื•ืช ื‘ื™ื•ืชืจ ื‘ื˜ื™ืคื•ืœ ื‘โ€“BOC ื”ืŸ ืื ืžื™ื” ืืฆืœ 49% ืžื”ืžื˜ื•ืคืœื™ื ื”ื›ื•ืœ ื‘ืกืš .)dysgeusia( 43%-37% ืืฆืœ ื‘ื—ื•ืฉ ื”ื˜ืขื ื•ื”ืคืจืขื•ืช ื”ืคืกืงืช ื˜ื™ืคื•ืœ ื‘ื’ืœืœ ืชื•ืคืขื•ืช ืœื•ื•ืื™ ื‘ื˜ื™ืคื•ืœ ื‘โ€“TPV ื”ื™ื™ืชื” ื‘ืฉื™ืขื•ืจ ืฉืœ 13%-20% ื•ื‘ื˜ื™ืคื•ืœ ื‘โ€“BOC ื‘ืฉื™ืขื•ืจ ืฉืœ 9%-19%. ื™ื—ื“ ืขื ื–ืืช, ืฉื™ืขื•ืจ ื”ืคืกืงืช TPV ื‘ืฉืœ ืชืคืจื—ืช ื”ื™ื” ื›โ€“5%-7% ื•ืจืง ืืฆืœ 1.5% ื”ื™ื” ืฆื•ืจืš ื‘ื”ืคืกืงืช ื›ืœ ื”ื˜ื™ืคื•ืœ, ื•ืื™ืœื• ื‘ื˜ื™ืคื•ืœ ื‘โ€“BOC ืืฆืœ 12%-16% ืžื›ืœืœ

ื”ื—ื•ืœื™ื ื”ื™ื” ืฆื•ืจืš ืœื”ืคืกื™ืง ื”ื˜ื™ืคื•ืœ, ืื•ืœื ืจืง ืืฆืœ 2% ื‘ืฉืœ ืื ืžื™ื”.

ืชื’ื•ื‘ื” ื‘ื™ืŸึพืชืจื•ืคืชื™ืช .CYP3A4 ืฉืชื™ ื”ืชืจื•ืคื•ืช ืขื•ื‘ืจื•ืช ืžื˜ื‘ื•ืœื™ื–ื ื‘ืžืขืจื›ืช ื”ืฆื™ื˜ื•ื›ืจื•ืžื™ืื ื•ืกืฃ ืœื›ืš, ื ืžืฆื ืฉื”ืชืจื•ืคื•ืช ืขืœื•ืœื•ืช ืœืขื›ื‘ ืชืจื•ืคื•ืช ื”ืžืชืคืจืงื•ืช ื‘ืžืขืจื›ืช ื–ื• ืื• ืฉืชืจื•ืคื•ืช ื”ืžืฉืคื™ืขื•ืช ืขืœ ืžืขืจื›ืช ื”โ€“CYP3A4 ืขืœื•ืœื•ืช ืœื”ืฉืคื™ืข ืขืœ ืจืžืช ื”โ€“DDAs. ื›ืš ืœืžืฉืœ ื ืžืฆื ืฉืฉื™ืžื•ืฉ ื‘โ€“TPV ืขืœื•ืœ tacrolimusโ€“ื‘ื“ื ืœืขืœื•ืช ืคื™ 4.6 ื•ืœืจืžืช ื” cyclosporineโ€“ืœื’ืจื•ื ืœืจืžืช ื”

ืชืคื™

ื’ื™ ื 

ื‘ื“ ื›

ืชืง

ื“ืœ ื‘

ื•ืœื™ืค

ื˜

ห† ื—ื•ืœื™ื ื ืื™ื‘ื™ื™ื ืœืœื ืฉื—ืžืช ื”ื›ื‘ื“ eRVR ืฉื”ืฉื™ื’ื•

ห† Null responders )ื‘ื˜ื™ืคื•ืœ ืงื•ื“ื(ห† ื—ื•ืœื™ื ืขื ืฉื—ืžืช ื”ื›ื‘ื“

ห† ื—ื•ืœื™ื ื ืื™ื‘ื™ื™ื ืœืœื ืฉื—ืžืช ื”ื›ื‘ื“ ืฉืœื ื”ืฉื™ื’ื• eRVR: ืžื“ื™ื“ ื‘ืฉื‘ื•ืข 8 ืืš ื‘ืœืชื™

ืžื“ื™ื“ ื‘ืฉื‘ื•ืข IU/ml <( 12ื•15-10( relapsers ื—ื•ืœื™ื ืœืœื ืฉื—ืžืช ื”ื›ื‘ื“ ืฉื”ื ห†

ืื• Partial responders )ื˜ื™ืคื•ืœ ืงื•ื“ื(

100 IU/mL < HCV RNA :)extended rapid virological response( eRVR .pegylated interferon-ฮฑื•ึพ ribavirin:PR ืœื˜ื™ืคื•ืœ. ื•ึพ24 8 ื‘ืฉื‘ื•ืข

boceprevir:BOC

ืขืฆื•ืจ ื˜ื™ืคื•ืœ

PRBOC+PR

BOC+PR

ืชืจืฉื™ื ืžืกืคืจ 1: ืื•ืคืŸ ื”ืฉื™ืžื•ืฉ ื‘ึพtelaprevir ื‘ืงืจื‘ ื—ื•ืœื™ ื–ื™ื”ื•ื ื›ืจื•ื ื™ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ื’ื ื•ื˜ื™ืค 1

ห† ื—ื•ืœื™ื ืœืœื ืฉื—ืžืช ื”ื›ื‘ื“, ื ืื™ื‘ื™ื™ื ืื• ืขื ื”ื™ืฉื ื•ืช ื–ื™ื”ื•ื ื‘ึพHCV ืœืื—ืจ )eRVR( ืฉื”ืฉื™ื’ื• ืชื’ื•ื‘ื” ื•ื™ืจื•ืœื•ื’ื™ืช ืžื•ืงื“ืžืช )relapsers( ื˜ื™ืคื•ืœ ืงื•ื“ื

eRVR ืฉืœื ื”ืฉื™ื’ื• relapsers ื—ื•ืœื™ื ืœืœื ืฉื—ืžืช ื”ื›ื‘ื“, ื ืื™ื‘ื™ื™ื ืื• ห† Partial and null responders ห†

ห† ื—ื•ืœื™ื ืขื ืฉื—ืžืช ื”ื›ื‘ื“

*eRVR HCV RNA :extended rapid virological response ื‘ืœืชื™ ืžื“ื™ื“ pegylatedื•ึพ PR ribavirin: ื•ึพ12 ืœื˜ื™ืคื•ืœ. 4 IU/mlื 10-15 ื‘ืฉื‘ื•ืข >

interferon-ฮฑ

ืขืฆื•ืจ ื˜ื™ืคื•ืœ

PR

PRTelaprevir +PR

ืื < IU/mLื•1000 ื‘ืฉื‘ื•ืข 4 ืื• 12:

ื”ืคืกืงืช ื›ืœ ื”ืชืจื•ืคื•ืช

ืฉื‘ื•ืขื•ืช4 12 24 36 480

HCV RNA ืื ื ื™ืชืŸ ืœืžื“ื™ื“ื”

PR ื‘ืฉื‘ื•ืข 24: ื”ืคืกืงืช

IU/mL 100 > ืื ื”ืคืกืง ื›ืœ ื”ืชืจื•ืคื•ืช

ืื ืžื“ื™ื“ IU/mL 15-10 >

ื”ืคืกืง ื›ืœ ื”ืชืจื•ืคื•ืช

ืฉื‘ื•ืขื•ืช4 48 12 24 28 28 360

HCV RNA

PR lead

inBOC+PR

Page 27: israel journal of the liver and related sciences

9

ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

44-24( ืžืฉืชื ื™ื ืœื–ืžื ื™ื )BOC/pegIFNฮฑ/RBV( ืžืฉื•ืœืฉ ื˜ื™ืคื•ืœ ื”ืžื—ืœื” ื—ื•ืžืจืช ื”ืžื•ืงื“ืžืช, ื”ื•ื•ื™ืจื•ืœื•ื’ื™ืช ื”ืชื’ื•ื‘ื” ืคื™ ืขืœ ืฉื‘ื•ืขื•ืช lead-in, ื”ื˜ื™ืคื•ืœ ื”ืžืฉื•ืœืฉ ืื™ืŸ ืฉืœื‘ TLVโ€“ื‘ ืงื•ื“ื(. ื˜ื™ืคื•ืœื™ ื•ื ื™ืกื™ื•ืŸ ื ืžืฉืš 12 ืฉื‘ื•ืขื•ืช ื•ืื—ืจื™ื• ื ื™ืชืŸ ื˜ื™ืคื•ืœ SOC ื‘ืžืฉืš ืคืจืง ื–ืžืŸ ืžืฉืชื ื” eRVR 36-12 ืฉื‘ื•ืขื•ืช ื ื•ืกืคื™ื(. ื‘ืงืจื‘ ื—ื•ืœื™ื ืœืœื ืฉื—ืžืช ืฉื”ื•ืฉื’ ืืฆืœื( )extended RVR( ืืคืฉืจ ืœืงืฆืจ ืืช ืžืฉืš ื”ื˜ื™ืคื•ืœ ื‘ืฉืชื™ ื”ืชืจื•ืคื•ืช. HCV RNA :ืžื•ื’ื“ืจ ื‘ื ืงื•ื“ื•ืช ื–ืžืŸ ืฉื•ื ื•ืช ืœื’ื‘ื™ ื›ืœ ืื—ืช ืžื”ืชืจื•ืคื•ืช eRVR(ื‘ืœืชื™ ืžื“ื™ื“ ื‘ืฉื‘ื•ืข 24-8 ื‘ืขืช ื˜ื™ืคื•ืœ ื‘โ€“BOC ื•ื‘ืฉื‘ื•ืข 4 ื•โ€“12 ื‘ื˜ื™ืคื•ืœ

.)TPVโ€“ื‘

ื—ื•ืœื™ื โ€œื ืื™ื‘ื™ื™ื" ืœื˜ื™ืคื•ืœ ืœืื—ืจื•ื ื” ืคื•ืจืกืžื• ืฉืชื•ืฆืื•ืชื™ื”ื ื”ื’ื“ื•ืœื™ื phase III ื‘ืžื—ืงืจื™ ,)ILLUMINATEโ€“ื•ื” ื—ื•ืœื™ื, 1,095 ืกื”"ื› ,ADVANCEโ€“ื” )ืžื—ืงืจื™ ื—ื•ืœื™ื ื‘ืงืจื‘ ืžืฉืžืขื•ืชื™ืช ื’ื‘ื•ื” ื”ื™ื” SVR ื”ืฉื’ืช ืฉืฉื™ืขื•ืจ ื ืžืฆื SOC ืฉืงื™ื‘ืœื• ื—ื•ืœื™ื ืœืขื•ืžืช TPV ืฉื›ืœืœ ืžืฉื•ืœืฉ ื˜ื™ืคื•ืœ ืฉืงื™ื‘ืœื• ืฉืงื™ืฆื•ืจ ื ืžืฆื ืขื•ื“ ื‘ื”ืชืืžื”. ,44% ืœืขื•ืžืช 75%-69% ื‘ืœื‘ื“: ืžืฉืš ื”ื˜ื™ืคื•ืœ ื”ื›ื•ืœืœ ืžโ€“48 ืฉื‘ื•ืขื•ืช ืœโ€“24 ืฉื‘ื•ืขื•ืช ืœื ืคื’ื ื‘ื”ืฉื’ืช SVR: 92% ืœืขื•ืžืช 88%. ื‘ืžื—ืงืจ ื”โ€“SPRINT-2 )ืกื”"ื› 1,097 ื—ื•ืœื™ื( ื”ื™ื” BOCโ€“ื‘ ืžืฉื•ืœืฉ ื˜ื™ืคื•ืœ ืฉืงื™ื‘ืœื• ื—ื•ืœื™ื ื‘ืงืจื‘ SVRโ€“ื” ืฉื™ืขื•ืจ

.SOC 63%-66% ืœืขื•ืžืช 37% ื‘ืงื‘ื•ืฆืช ื”ื‘ื™ืงื•ืจืช ืฉืงื™ื‘ืœื”

ื—ื•ืœื™ื โ€œืžื ื•ืกื™ื" ืฉื ื›ืฉืœื• ื‘ื”ืฉื’ืช SVR ื‘ื˜ื™ืคื•ืœ ืงื•ื“ื relapsers, partial( "ืฉื›ืœืœ 662 ื—ื•ืœื™ื โ€œืžื ื•ืกื™ื REALIZEโ€“ื‘ืžื—ืงืจ ื”responders, null responders(, ื›ืœ ื”ื—ื•ืœื™ื ืงื™ื‘ืœื• ื˜ื™ืคื•ืœ ื‘ืžืฉืš 48 ืฉื‘ื•ืขื•ืช. ืืฆืœ ื›ืœ ื”ื—ื•ืœื™ื ืฉืงื™ื‘ืœื• TPV ืฉื™ืขื•ืจ ื”โ€“SVR ื”ื™ื” 64%-66% 88%-83% relapsersโ€“ืœืขื•ืžืช 17% ื‘ืงื‘ื•ืฆืช ื”ื‘ื™ืงื•ืจืช )ื‘ืงื‘ื•ืฆืช ื” partial respondersโ€“ื” ื‘ืงื‘ื•ืฆืช ื”ื‘ื™ืงื•ืจืช, ื‘ืงื‘ื•ืฆืช 24% ืœืขื•ืžืช 33%-29% null respondersโ€“54%-59% ืœืขื•ืžืช 15% ื•ื‘ืงื‘ื•ืฆืช ื”ืœืขื•ืžืช 5%(. ืžืžื—ืงืจ ื–ื” ืืคืฉืจ ืœืœืžื•ื“ ื›ื™ ื˜ื™ืคื•ืœ ื—ื•ื–ืจ ื‘โ€“TPV ื‘ืงื‘ื•ืฆืช ื—ื•ืœื™ื ื–ื• ืฉื™ืคืจ ืืช ืฉื™ืขื•ืจ ื”ืฉื’ืช ื”โ€“SVR ื‘ืื•ืคืŸ ื ื™ื›ืจ )ื‘โ€“24%-64%( ื•ื›ื™

ืฉื™ืžื•ืฉ ื‘โ€“lead-in phase - ื‘ื˜ื™ืคื•ืœ ื‘โ€“TPV ืื™ื ื• ืžื•ืกื™ืฃ ื“ื‘ืจ. ื‘ืžื—ืงืจ ื”โ€“RESPOND-2 )403 ื—ื•ืœื™ื ืขื ื’ื ื•ื˜ื™ืค 1( ื”ืฉื™ืœื•ื‘ ืฉืœ BOC ื‘ื˜ื™ืคื•ืœ ื”ื•ื‘ื™ืœ ืœืฉื™ืคื•ืจ ื ื™ื›ืจ ื‘ื”ืฉื’ืช SVR: 69%-75% ื‘ืงื‘ื•ืฆืช ื”โ€“relapsers ื•โ€“40%-52% ื‘ืงื‘ื•ืฆืช ื”โ€“partial responders ืœืขื•ืžืช 29%

ื•โ€“7% ื‘ืงื‘ื•ืฆื•ืช ื”ื‘ื™ืงื•ืจืช, ื‘ื”ืชืืžื”.

ืื•ืคืŸ ื”ืฉื™ืžื•ืฉ ื‘ืชืจื•ืคื•ืช ื”ืื ื˜ื™ึพื•ื™ืจืืœื™ื•ืช ื”ื™ืฉื™ืจื•ืช

EMAื•ื‘ึพ FDAืขืœ ืคื™ ืจื™ืฉื•ืžืŸ ื‘ึพื–ืžืŸ ืœื”ืคืกืงื” ื•โ€“BOC, ื›ื•ืœืœ ื ืงื•ื“ื•ืช TPV ื”ื˜ื™ืคื•ืœ ื‘ืฉืชื™ ื”ืชืจื•ืคื•ืช, ืžื•ืงื“ืžืช ืฉืœ ื”ื˜ื™ืคื•ืœ )stopping rules( ื•ืœื”ื—ืœื˜ื•ืช ืœื’ื‘ื™ ื˜ื™ืคื•ืœ ืžื•ื ื—ื” ืชื’ื•ื‘ื” )RGT(. ื ืงื•ื“ื•ืช ื”ื–ืžืŸ ืœื›ืœ ืื—ืช ืžื”ืชืจื•ืคื•ืช ื”ืŸ ืฉื•ื ื•ืช. ืžื˜ืจืชื” ืฉืœ ื”ืคืกืงืช ื˜ื™ืคื•ืœ ืžื•ืงื“ืžืช ื”ื™ื ืœืžื ื•ืข ื”ืชืคืชื—ื•ืช ื–ื ื™ื ืขืžื™ื“ื™ื ืฉืœ ื•ื›ืŸ ืœืžื ื•ืข ื—ืฉื™ืคื” ืžื™ื•ืชืจืช ืœืชื•ืคืขื•ืช ืœื•ื•ืื™ ื”ื ื’ื™ืฃ ืชื•ืš ื›ื“ื™ ื˜ื™ืคื•ืœ, ื›ืืฉืจ ื”ืกื™ื›ื•ื™ ืœื”ืฉื™ื’ SVR ื”ื•ื ื–ื ื™ื—. ืื•ืคืŸ ื”ืฉื™ืžื•ืฉ ื‘ืฉืชื™ ื”ืชืจื•ืคื•ืช ืžื•ืฆื’ ื‘ืชืจืฉื™ื ืžืกืคืจ 1, ื•ืžืคืืช ืงื•ืฆืจ ื”ื™ืจื™ืขื” ืœื ืืคืจื˜ ืžืขื‘ืจ ืœื›ืš ื‘ืžืกื’ืจืช ืขื“ื›ื•ืŸ ื–ื”. ืจืื•ื™ ืœืฆื™ื™ืŸ ืฉืœื’ื‘ื™ BOC ื”ื”ื ื—ื™ื•ืช ืœื˜ื™ืคื•ืœ ื‘ื—ื•ืœื™ื EMAโ€“ื•ื” FDAโ€“ืฉื•ื ื•ืช ื‘ืจื™ืฉื•ื ื” eRVR ืžื ื•ืกื™ื" ืœืœื ืฉื—ืžืช ืฉื”ืฉื™ื’ื•โ€œ)ื‘ืจื™ืฉื•ื ื‘โ€“FDA ื”ื˜ื™ืคื•ืœ ื”ืžืฉื•ืœืฉ ื™ื™ืžืฉืš 32 ืฉื‘ื•ืขื•ืช ื•ื™ื•ืคืกืง ืœืื—ืจ 36 ืฉื‘ื•ืขื•ืช ืฉืœ ื˜ื™ืคื•ืœ ื›ื•ืœืœ, ืืช ื”ื ื—ื™ื•ืช ื”โ€“EMA ืœื˜ื™ืคื•ืœ ืืคืฉืจ ืœืจืื•ืช

ื‘ืชืจืฉื™ื ืžืกืคืจ 1(.

ื”ืขืจื•ืช ื•ื”ืืจื•ืช: ืื™ืœื• ื—ื•ืœื™ื โ€œื™ื™ื”ื ื•" ืžื˜ื™ืคื•ืœ?

ืื™ืŸ ืกืคืง ืฉืื ื• ืขื•ืžื“ื™ื ื‘ืคืชื—ื” ืฉืœ ืชืงื•ืคื” ื—ื“ืฉื”, ื•ื‘ื” ืจื•ื‘ ื—ื•ืœื™ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ื”ืžืชืื™ืžื™ื ืœื˜ื™ืคื•ืœ ื™ื•ื›ืœื• ืœื™ื”ื ื•ืช ืžื˜ื™ืคื•ืœ ื™ืขื™ืœ ื™ื•ืชืจ ืžืฉืžืขื•ืชื™ืช ืžื”ื˜ื™ืคื•ืœ ื›ื™ื•ื. ืœื’ื‘ื™ ื—ืœืง ืžื”ื—ื•ืœื™ื ื”ื˜ื™ืคื•ืœ ื™ื”ื™ื” ืืฃ ืงืฆืจ ื™ื•ืฆืจ ื‘ืขื™ื•ืช ื—ื“ืฉื•ืช ื”ืงืฉื•ืจื•ืช ื™ื•ืชืจ. ืื•ืœื ืฉื™ืœื•ื‘ ื”โ€“DAAs ื‘ื˜ื™ืคื•ืœ ืœืชื•ืคืขื•ืช ืœื•ื•ืื™ ื ื•ืกืคื•ืช, ืœืžื•ืจื›ื‘ื•ืช ื”ืคืจื•ื˜ื•ืงื•ืœื™ื ื”ื˜ื™ืคื•ืœื™ื™ื, ืœื ื™ื˜ื•ืจ ืžืกื•ื‘ืš ื™ื•ืชืจ ืฉืœ ื”ื˜ื™ืคื•ืœ, ืœืชื’ื•ื‘ื•ืช ื‘ื™ืŸโ€“ืชืจื•ืคืชื™ื•ืช, ืœื”ืชืžื•ื“ื“ื•ืช ืขื ื‘ืขื™ื™ืช ื”ื”ื™ืขื ื•ืช ืœื˜ื™ืคื•ืœ ื”ืžื•ืจื›ื‘, ืœื”ื•ืคืขืช ืขืžื™ื“ื•ืช ืœืชืจื•ืคื•ืช ื”ื—ื“ืฉื•ืช ื”ื’ื‘ื•ื” ื”ืžื—ื™ืจ ื‘ืฉืœ ื”ื‘ืจื™ืื•ืช ืžืขืจื›ืช ืขืœ ื›ืœื›ืœื™ ืœืขื•ืžืก ื•ื›ืžื•ื‘ืŸ ื”ื›ืจื•ืš ื‘ืฉื™ืžื•ืฉ ื‘ืชืจื•ืคื•ืช ืืœื•. ื™ืฉ ืœื–ื›ื•ืจ ืฉื™ื”ื™ื• ื—ื•ืœื™ื ืฉืœื ื™ื–ื“ืงืงื• ืœื˜ื™ืคื•ืœ ื”ืžืฉื•ืœื‘ ื•ื™ื•ื›ืœื• ืœื”ืฉื™ื’ SVR ื‘ืฉื™ืขื•ืจ ื’ื‘ื•ื” ืžืื•ื“ )ื›โ€“85%-90%( ื‘ืืžืฆืขื•ืช ื˜ื™ืคื•ืœ ื‘โ€“SOC ื‘ืœื‘ื“. ืืœื” ืื•ืชื ื—ื•ืœื™ื ืฉื”ืฉื™ื’ื• ืชื’ื•ื‘ื” ื•ื™ืจื•ืœื•ื’ื™ืช ืžื”ื™ืจื” )RVR( ืœืื—ืจ 4 ืฉื‘ื•ืขื•ืช ื˜ื™ืคื•ืœ ื‘โ€“SOC, ื•ื‘ืžื™ื•ื—ื“ ืืœื”

.C/C ื’ื ื•ื˜ื™ืค IL28B ืขืืœืจื•ืข ื”ืžื–ืœ, ืจืง 10%-15% ืžื”ื—ื•ืœื™ื ืขื•ื ื™ื ืœืงืจื™ื˜ืจื™ื•ื ื™ื ืืœื”. ื›ืžื• ื›ืŸ, ืื™ืŸ ืฆื•ืจืš ืœื˜ืคืœ ื‘ืื•ืคืŸ ืžื™ื™ื“ื™ ื‘ื˜ื™ืคื•ืœ ื”ืžืฉื•ืœื‘ ื‘ื—ื•ืœื™ื ืฆืขื™ืจื™ื ืœืœื ืžื—ืœื•ืช ืจืงืข ืžืฉืžืขื•ืชื™ื•ืช ื•ืœืœื ืคื™ื‘ืจื•ื–ื™ืก ืžืฉืžืขื•ืชื™ ื•ืืคืฉืจ ืœื ืกื•ืช ืœื˜ืคืœ ื‘ื—ื•ืœื™ื ืืœื• ื‘โ€“SOC. ืืคืฉืจื•ืช ืกื‘ื™ืจื” ื ื•ืกืคืช ืขื‘ื•ืจ ื—ื•ืœื™ื ืืœื”, ืฉืœื ืฆืคื•ื™ื” ื”ื—ืžืจื” ืžื”ื™ืจื” ื‘ืžื—ืœืชื, ื”ื™ื ื”ืžืชื ื” ืฉืœ 3-2 ืฉื ื™ื ืขื“ ืœื”ื•ืคืขืช ื˜ื™ืคื•ืœ ืกื‘ื™ืœ ื™ื•ืชืจ, ืฉืคืจื•ืคื™ืœ ื”ืขืžื™ื“ื•ืช ืฉืœื• ื™ื”ื™ื” ื˜ื•ื‘ ื™ื•ืชืจ ื•ืฉืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ืžืžื ื• ื™ื”ื™ื• ืžื•ืขื˜ื•ืช, ื•ืื•ืœื™ ื”ื•ื ืืฃ ื™ื›ืœื•ืœ ืฉื™ืœื•ื‘ ืฉืœ

ื›ืžื” ืชืจื•ืคื•ืช. ืื™ืŸ ืกืคืง ืฉื—ื•ืœื™ื ื”ื–ืงื•ืงื™ื ืœื˜ื™ืคื•ืœ ื‘โ€“DAAs ื›ืขืช ื”ื ืืœื” ื”ืกื•ื‘ืœื™ื ืžืคื™ื‘ืจื•ื–ื™ืก ืžืชืงื“ื )F3/F4(, ื•ื‘ืคืจื˜ ื—ื•ืœื™ื ืฉื ืจืื™ื ืืฆืœื ื’ื•ืจืžื™ื SOCโ€“ื”ืงืฉื•ืจื™ื ืœืชื’ื•ื‘ื” ื•ื™ืจื•ืœื•ื’ื™ืช ื ืžื•ื›ื”, ืžืื—ืจ ืฉืกื™ื›ื•ื™ื™ื”ื ืœื”ื’ื™ื‘ ืœื ืžื•ื›ื™ื ื•ืžื—ืœืชื ืขืœื•ืœื” ืœื”ืชืงื“ื ื•ืœื”ืกืชื‘ืš ืชื•ืš ืฉื ื™ื ืกืคื•ืจื•ืช. ื‘ื™ืŸ ืืœื” ื ื›ืœืœื™ื ื’ื ื—ื•ืœื™ื ืฉื”ื•ื’ื“ืจื• null responders. ืœื—ื•ืœื™ื ืืœื• ืกื™ื›ื•ื™ ื ืžื•ืš ืœื”ืฉื™ื’ SVR )30% ื‘ืœื‘ื“ ืขืœ ืคื™ ืžื—ืงืจ ื”โ€“REALIZE(, ืื•ืœื ื›ืขืช ืื™ืŸ ืืคืฉืจื•ืช ื˜ื•ื‘ื” ืžื–ื• ืขื‘ื•ืจื. ื ื•ืกืฃ ืœื›ืš, ืจืื•ื™ ืœื”ื–ื›ื™ืจ ื›ื™ ืžืื—ืจ ืฉื‘ืฉืœื‘ ื–ื” ื™ืขื™ืœื•ืช ืžืขื›ื‘ื™ ื”ืคืจื•ื˜ื™ืื–ื” ื”ื ื•ื›ื—ื™ื™ื ืžื•ื’ื‘ืœืช ืื• ื—ืกืจื” ืœื’ื‘ื™ ื’ื ื•ื˜ื™ืคื™ื ืฉื•ื ื™ื ืžื’ื ื•ื˜ื™ืค 1, ื”ืจื™ ืฉื›ืœ ื”ื—ื•ืœื™ื ืขื ื’ื ื•ื˜ื™ืค 2 ื•โ€“3 ืžื•ืขืžื“ื™ื ืœื˜ื™ืคื•ืœ ื‘โ€“SOC. ื™ื—ื“ ืขื ื–ืืช, ื‘ืขืชื™ื“ ื”ืงืจื•ื‘ ื—ืœืง ืžื”โ€“DAAs ื™ืคืขืœื• ื ื’ื“

ื›ืœ ื”ื’ื ื•ื˜ื™ืคื™ื ื•ืืคืฉืจื•ื™ื•ืช ื”ื˜ื™ืคื•ืœ ืชืฉืชื ื™ื ื”.

ื˜ื‘ืœื” ืžืกืคืจ 2: ื”ืงื‘ื•ืฆื•ืช ื”ืฉื•ื ื•ืช ืฉืœ ื”ืชืจื•ืคื•ืช )DAAs( ื”ืื ื˜ื™ึพื•ื™ืจืืœื™ื•ืช ื”ื™ืฉื™ืจื•ืช

*ื”ืฉื•ื•ืื” ืื™ื›ื•ืชื™ืช ื‘ื™ืŸ ืงื‘ื•ืฆื•ืช ื”ืชืจื•ืคื•ืช ื”ืฉื•ื ื•ืช: +ื—ืœืฉ, ++ื‘ื™ื ื•ื ื™, +++ื—ื–ืง

ื™ืขื™ืœื•ืช ืื ื˜ื™ ื•ื™ืจืืœื™ืช

ื˜ื•ื•ื— ื™ืขื™ืœื•ืช ื‘ื’ื ื•ื˜ื™ืคื™ื

ื•ื™ืจืืœื™ื™ื ืฉื•ื ื™ื

ืžื—ืกื•ื ื‘ืคื ื™ ื”ืชืคืชื—ื•ืช

ื–ื ื™ื ืขืžื™ื“ื™ื

NS3/4Aprotease inhibitors +++ + ++/+

NS5A inhibitors +++ ++/+ ++/+

NS5B (nucleosides) ++/+ +++ +++

NS5B (non-nucleosides) ++/+ + +

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ืžืจืฅ 2012

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”

ื‘ื˜ื™ืคื•ืœ ื‘ ืžืฉืžืขื•ืชื™ ืฉื™ื ื•ื™ ื—ืœ ืœื ื”ืื—ืจื•ืŸ ื”ืขืฉื•ืจ ืžื”ืœืš ื‘ืฉื™ืขื•ืจื™ ืื• ื ื’ื™ืคื™ืช ื›ื‘ื“ ื‘ื“ืœืงืช ื”ื›ืจื•ื ื™ ื”ื ื’ื™ืคื™ ื‘ื–ื™ื”ื•ื 1 ื‘ื’ื ื•ื˜ื™ืค ืžื“ื•ื‘ืจ ื›ืืฉืจ ื•ื‘ืžื™ื•ื—ื“ ืžืžื ื•, ื”ื”ื—ืœืžื” ]4-1[. ื‘ืฉื ื™ื ื”ืื—ืจื•ื ื•ืช ื”ื•ืฉืงืข ืžืืžืฅ ืจื‘ ื‘ืคื™ืชื•ื— ืชืจื•ืคื•ืช ืื ื˜ื™โ€“

ื•ื™ืจืืœื™ื•ืช ื”ืคื•ืขืœื•ืช ื™ืฉื™ืจื•ืช ื ื’ื“ ืืชืจื™ื ื”ื—ื™ื•ื ื™ื™ื ืœืžืขื’ืœ ื”ื—ื™ื™ื ืฉืœ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช )direct acting antiviral agents - DAAs(, ืžื” ืฉื”ื•ื‘ื™ืœ ืœืคืจื™ืฆืช ื”ื“ืจืš ื”ืžืžืฉื™ืช ื”ื’ื“ื•ืœื” ื‘ื™ื•ืชืจ ืžืื– ื–ื•ื”ื” ื”ื ื’ื™ืฃ ืœืจืืฉื•ื ื” ื‘โ€“1989 ื•ืœืžื”ืคื›ื” ืืžืชื™ืช ื‘ื˜ื™ืคื•ืœ ื‘ื–ื™ื”ื•ื ื”ื›ืจื•ื ื™ ื•ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืžืกื•ื’ ื”ืคื™ื˜ื™ื˜ื™ืก C. ืฉืชื™ ื”ืชืจื•ืคื•ืช ื”ืจืืฉื•ื ื•ืช ืžืกื•ื’ ื–ื” ื”ืŸ ืžืงื‘ื•ืฆืช NS3 - serine protease inhibitors( NS3/4A ืื• ืžืขื›ื‘ื™ ื”ืคืจื•ื˜ื™ืื–ื” incivoยฎ( telaprevir :)PI( ื•โ€“boceprevir )ยฎvictrelis(. ื”โ€“FDA ื”ืืžืจื™ืงืื™ ื•ื”โ€“EMAื )European Medicines Agency( ืื™ืฉืจื• ืืช ื”ืฉื™ืžื•ืฉ ื‘ืฉืชื™

ื•ื”ืŸ ื ื›ืœืœื•ืช ื‘ื˜ื™ืคื•ืœ ื•ื‘ื™ื•ื ื™ 2011, ื‘ื”ืชืืžื”, ื”ืชืจื•ืคื•ืช ื”ืœืœื• ื‘ืžืื™ ืงื• ืจืืฉื•ืŸ ืœื–ื™ื”ื•ื ื›ืจื•ื ื™ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืžืกื•ื’ ื”ืคื˜ื™ื˜ื™ืก C ื’ื ื•ื˜ื™ืค 1 ื‘ืืจื”"ื‘ ื•ื‘ื—ืœืง ืžืืจืฆื•ืช ืื™ืจื•ืคื”. ื”ื—ืœ ืžโ€“2012 ื ื›ืœืœื•ืช ืชืจื•ืคื•ืช ืืœื” ื‘"ืกืœ ื”ืชืจื•ืคื•ืช" ื‘ื™ืฉืจืืœ ืœื’ื ื•ื˜ื™ืค 1 ื‘ื”ืชื•ื•ื™ื•ืช ืžืกื•ื™ืžื•ืช )ื“ืจื’ืช )treatment-naive( "ื”ืŸ ืขื‘ื•ืจ ื—ื•ืœื™ื โ€œื ืื™ื‘ื™ื™ื )2 ืคื™ื‘ืจื•ื–ื™ืก ื›ื‘ื“ื™ืช โ‰ค ื•ื”ืŸ ืขื‘ื•ืจ ื—ื•ืœื™ื โ€œืžื ื•ืกื™ื" )treatment-experienced( ืฉืœื ื”ืฆืœื™ื—ื• ื‘ื˜ื™ืคื•ืœ )sustained virological response(ื SVR ืืฆืœื ืœื”ืฉื™ื’ ื”ืขื•ื‘ื“ื” ืขืฆื ืงื•ื“ื. ืื ื˜ื™โ€“ื•ื™ืจืืœื™ NS5Bโ€“ื•ืœ NS3-serine proteaseโ€“ืฉืœ RNA-dependent RNA polymeraseื‘ืชื”ืœื™ืš ื—ื™ื•ื ื™ ืชืคืงื™ื“ ื™ืฉ )RdRp(ืฉืœ ื”ื—ื™ื™ื ื•ื‘ืžืขื’ืœ ื”ืจืคืœื™ืงืฆื™ื” ืœืžื•ืงื“ ืื•ืชื ื”ืคื›ื” ,]4[ ื”ื ื’ื™ืฃ ื”ืžืืžืฅ ืขื™ืงืจ ืžืจื•ื›ื– ื”ื™ื” ืฉื‘ื• ื”ืจืืฉื•ื ื™. ื‘ืฉืœื‘ื™ ืžื—ืงืจ ืžื•ืงื“ืžื™ื ื”ืžื›ื•ื•ื ื•ืช ืชืจื•ืคื•ืช ื ืžืฆืื• ื™ื•ืชืจ ืœืžืจื›ื™ื‘ื™ ื ื’ื™ืฃ ืื—ืจื™ื ืื• ืœืžื˜ืจื•ืช ื•ืืฉืจ ื”ืžืื›ืกืŸ ื‘ืชื ื”ืงืฉื•ืจื•ืช ืœื‘ื™ืŸ ื‘ื™ื ื• ืœืื™ื ื˜ืจืืงืฆื™ื” ื—ืฉื•ื‘ื•ืช ื›โ€“50 ืชืจื•ืคื•ืช ืฉื•ื ื•ืช ื›ื™ื•ื ื”ื ื’ื™ืฃ. ืฉื•ื ื™ื ืžื—ืงืจ ื‘ืฉืœื‘ื™ ื ืžืฆืื•ืช ื›ื•ืœืœื•ืช ื•ืืœื• )1 ืžืกืคืจ )ื˜ื‘ืœื” ืžืขื›ื‘ื™ื ืื ื˜ื™โ€“ื•ื™ืจืืœื™ื™ื ื™ืฉื™ืจื™ื ื›ืžื• ,NS3/4A-protease inhibitorsโ€“ื” non-nucleosideโ€“ื• nucleoside( NS5B-polymerase inhibitorsโ€“ื”inhibitors( ื•ื”โ€“NS5A-inhibitors. ื”ืงื‘ื•ืฆื•ืช ื”ืฉื•ื ื•ืช ื ื‘ื“ืœื•ืช ื‘ื™ืขื™ืœื•ืช ื•ื‘ื˜ื•ื•ื— ื–ื ื™ื ืขืžื™ื“ื™ื ื”ืคืขื™ืœื•ืช ื”ืื ื˜ื™โ€“ื•ื™ืจืืœื™ืช, ื‘ืจื’ื™ืฉื•ืช ืœื”ื•ืคืขืช ื”ืคืขื™ืœื•ืช ื ื’ื“ ื’ื ื•ื˜ื™ืคื™ื ืฉื•ื ื™ื ืฉืœ ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช )ื˜ื‘ืœื” ืžืกืคืจ 2(.

ื”ื˜ื™ืคื•ืœ ื‘ืชืจื•ืคื•ืช ื”ืื ื˜ื™ึพื•ื™ืจืืœื™ื•ืช )DAAs( ื”ื™ืฉื™ืจื•ืช

ื‘ืชืจื•ืคื•ืช ืžื•ื ื•โ€“ืชืจืืคื™ ื˜ื™ืคื•ืœ ื›ื™ ื”ืกืชื‘ืจ ื‘ืžื—ืงืจ ืžื•ืงื“ื ื‘ืฉืœื‘ ืื—ื“ื™ื, ื˜ื™ืคื•ืœ ื™ืžื™ ืœืื—ืจ ื›ื‘ืจ ืขืžื™ื“ื™ื ื–ื ื™ื ืœื”ื•ืคืขืช ืžื•ื‘ื™ืœ ืืœื” ื”ื”ื™ืฉื ื•ืช ืฉื™ืขื•ืจ ืืช ื”ื˜ื™ืคื•ืœ ืžืขืœื” ืจื™ื‘ื•ื™ืจื™ืŸ ืžืคืจื•ื˜ื•ืงื•ืœ ื•ื”ื•ืจื“ืช ืฉืœ ื”ืžื—ืœื”, ื•ืœื›ืŸ ืฉืœื“ ื”ื˜ื™ืคื•ืœ ื ืฉืืจ ื”โ€“SOCื )pegIFNฮฑ/RBV( ืœโ€“48 ื‘ืขื™ืงืจ ื™ืขื™ืœื•ืช ื”ืชืจื•ืคื•ืช 2 ืœื›ืš, ื ื•ืกืฃ ื›ื•ืœืœ. ื˜ื™ืคื•ืœ ืฉืœ ืฉื‘ื•ืขื•ืช ื‘ื’ื ื•ื˜ื™ืค ืœื˜ื™ืคื•ืœ ื™ืขื™ืœื•ืช ืœื ื›ืœืœ ื•ืืฃ ื•ืคื—ื•ืช 1 ื‘ื’ื ื•ื˜ื™ืค ืœื˜ื™ืคื•ืœ ื™ืฉ ืฉืœื‘ BOCโ€“ื‘ ื‘ื˜ื™ืคื•ืœ ื”ืชืจื•ืคื•ืช: 2 ื‘ื™ืŸ ืฉื•ื ื™ ื™ืฉ .3 ื•ื‘ื’ื ื•ื˜ื™ืค 2lead-in ืฉืœ 4 ืฉื‘ื•ืขื•ืช ืฉื‘ื”ื ื ื™ืชืŸ ื˜ื™ืคื•ืœ ื‘โ€“SOC, ื•ืœืื—ืจ ืžื›ืŸ ื ื™ืชืŸ

ื”ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช 2012: ืคืจื™ืฆืช ื“ืจืš

ืืœื™ ืฆื•ืงืจืžืŸื”ื™ื—ื™ื“ื” ืœืžื—ืœื•ืช ื›ื‘ื“, ืžื—ื•ื– ื—ื™ืคื” ื•ื’ืœื™ืœ ืžืขืจื‘ื™ ื•ืžืจื›ื– ืจืคื•ืื™ ื›ืจืžืœ, ืฉื™ืจื•ืชื™ ื‘ืจื™ืื•ืช ื›ืœืœื™ืช

ืžืขื›ื‘ื™ ื”ืคืจื•ื˜ื™ืื–ื•ืช ืžื”ื“ื•ืจ ื”ืจืืฉื•ืŸ

ื”ื‘ื™ืื• ืœืžื”ืคื™ื›ื” ื‘ื˜ื™ืคื•ืœ ื‘ื”ืคื˜ื™ื˜ื™ืก C ื’ื ื•ื˜ื™ืค 1 ืœืขื•ืžืช

ื”ื˜ื™ืคื•ืœ ื”ืžืงื•ื‘ืœ ืขื“ ื›ื”: ืฉื™ืคื•ืจ ื‘ืฉื™ืขื•ืจ

30% ื‘ื”ืฉื’ืช ื”ื—ืœืžื” ืžื”ื–ื™ื”ื•ื

ื”ื ื’ื™ืคื™ ื‘ื—ื•ืœื™ื โ€œื ืื™ื‘ื™ืโ€œ ืœื˜ื™ืคื•ืœ

ืงื•ื“ื ื•ื‘ืฉื™ืขื•ืจ 24%-64% ื‘ื—ื•ืœื™ื

ืฉื ื›ืฉืœื• ืœื”ื’ื™ื‘ ืœื˜ื™ืคื•ืœ ืงื•ื“ื

ืชืคื™

ื’ื™ ื 

ื‘ื“ ื›

ืชืง

ื“ืœ ื‘

ื•ืœื™ืค

ื˜

ื˜ื‘ืœื” ืžืกืคืจ 1: ืชืจื•ืคื•ืช ืื ื˜ื™ึพื•ื™ืจืืœื™ื•ืช ื™ืฉื™ืจื•ืช )Direct Acting Antiviral Agents(

ื‘ืฉืœื‘ื™ื ืฉื•ื ื™ื ืฉืœ ืžื—ืงืจ ื•ืคื™ืชื•ื—

Select DAAs in Clinical Development

Phase I Phase II Phase III

Protease Inhibitor

ACH- 1625GS 9451MK-5712VX-985PHX1766

BMS-650032 (asunaprevir)CTS-1027RG7227 (Danoprevir)GS9256IDX320MK7009 (Vaniprevir)ABT-450

BI201335TMC435BoceprevirTelaprevir

Non-nucleoside polymerase inhibitors

BI 207127IDX375VX759GS9190

ABT-333ABT-072ANA598BMS-791325PF00868554 (Filibuvir)TegobuvirVCH-759VCH-222MK3281

NucleosidePolymerase inhibitors

RG7348MK0608

IDX184PSI-7977RG 7128 (mericitabine)

NS5A inhibitors

A-831PPI-461GS2336805

BMS-790052BMS-824393CF102AZD7297

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ืืฉื›ื ื–ื™ )M645R ,E1064A ื•โ€“H1069Q( ืžื•ื‘ื™ืœื” ืœื–ื™ื”ื•ื™ ืฉืœ 87% ืžื”ืžืงืจื™ื. 4 ื”ืžื•ื˜ืฆื™ื•ืช ื”ื ื•ืชืจื•ืช )M885I ,H1207R ,G1281D ื•ืื—ืช ืฉืœื ื–ื•ื”ืชื”( ื ืžืฆืื• ื›ืœ ืื—ืช ืืฆืœ ื—ื•ืœื” ื™ื—ื™ื“, ื•ื”ืžื•ื˜ืฆื™ื•ืช ื”ืฉื›ื™ื—ื•ืช ื‘ืื•ื›ืœื•ืกื™ื™ื” ื–ื•

ืžืฉืžืฉื•ืช ื›ื’ืœืื™ ื”ืžืขืœื” ืขืœ ืคื ื™ ื”ืฉื˜ื— ืืช ื”ืžื•ื˜ืฆื™ื•ืช ื”ื ื“ื™ืจื•ืช. ื‘ืกืงืจ ืฉืœ ื‘ื•ื ื”โ€“ืชืžื™ืจ ืžืฉื ืช 1990 ืจืง ืžืฉืคื—ื” ืื—ืช ืžืชื•ืš 21 )4.8%( ื”ื™ื™ืชื” ืžืžื•ืฆื ืืฉื›ื ื–ื™, ื•ื‘ืขื‘ื•ื“ืชื• ืฉืœ ืงืœื™ื ืกืงื™ ืžืฉื ืช 1998 ืจืง

3 ื ื‘ื“ืงื™ื ื”ื™ื• ืžืžื•ืฆื ืืฉื›ื ื–ื™. ืœืขื•ืžืช ื–ืืช, ื‘ืขื‘ื•ื“ื” ืฉืœ ืคื–ื•ื•ืœ ื•ืขืžื™ืชื™ื• ืžืฉื ืช 1977, 9 ืžืชื•ืš 29 ืžืฉืคื—ื•ืช )31%( ื”ื™ื• ืžืžื•ืฆื

ืืฉื›ื ื–ื™. ืคื–ื•ื•ืœ ืฉืœ ืœืขื‘ื•ื“ื•ืช ื‘ื ื™ื’ื•ื“ ื•ืขืžื™ืชื™ื• ื•ืฉืœ ื‘ื•ื ื”โ€“ืชืžื™ืจ ื•ืขืžื™ืชื™ื” ืžื›ื•ื•ืŸ ื ืขืฉื” ืžืืžืฅ ]3[, ืฉื‘ื”ืŸ ืœืืชืจ ื—ื•ืœื™ื ื‘ืžื—ืœื” ืขืœโ€“ื™ื“ื™ ืคื ื™ื™ื” ื™ื–ื•ืžื” ืœื™ื—ื™ื“ื•ืช ื”ื›ื‘ื“ ื•ืœืžื—ืœืงื•ืช ื‘ืืจืฅ, ื”ืฉื•ื ื•ืช ื”ื ื•ื™ืจื•ืœื•ื’ื™ื•ืช ืžืฉืงืคื™ื ื–ื• ื‘ืขื‘ื•ื“ื” ื”ื ืชื•ื ื™ื ืžื•ืžื—ื™ื ืฉืœ ื™ื–ื•ืžื•ืช ื”ืคื ื™ื•ืช ืฉื•ื ื™ื, ื•ืคื ื™ื•ืช ืขืฆืžื™ื•ืช ืฉืœ ื—ื•ืœื™ื, ื•ื‘ืื” ืœื™ื“ื™ ื‘ื™ื˜ื•ื™ ื’ื ื™ื›ื•ืœืชื ืฉืœ

ื ื‘ื“ืงื™ื ืฉืœื ื–ื›ื• ืœืžื™ืžื•ืŸ ื”ืงื•ืคื•ืช ืœืฉืœื ืžื›ื™ืกื ืขื‘ื•ืจ ื”ื‘ื“ื™ืงื”. 17 ืžืชื•ืš 34 ื”ื ื‘ื“ืงื™ื ื‘ืขื‘ื•ื“ื” ื–ื• ื”ื ืžืžื•ืฆื ืืฉื›ื ื–ื™ ื•ืžืฉืชื™ื™ื›ื™ื ืœโ€“14 ืžืฉืคื—ื•ืช. ืืฃ ืขืœ ืคื™ ืฉื”ื ืชื•ื ื™ื ืื™ื ื ืžืืคืฉืจื™ื ืœื—ืฉื‘ ืืช ืฉื›ื™ื—ื•ืช ื”ื ืฉืื•ืช ื‘ืขื“ื” ื–ื•, ื”ื ืชื•ื ื™ื ืฉื ืืกืคื• ืขืœโ€“ื™ื“ื™ ืคื–ื•ื•ืœ ื•ืขืžื™ืชื™ื• ืžืขื™ื“ื™ื ืขืœ ื›ืš

ืฉืฉื›ื™ื—ื•ืช ื”ื ืฉืื•ืช ื‘ืงืจื‘ ืืฉื›ื ื–ื™ื ื’ื‘ื•ื”ื” ืžืฉืกื‘ืจื• ื‘ืขื‘ืจ. .H1069Q ื›ืœ ื”ื™ื”ื•ื“ื™ื ื™ื•ืฆืื™ ืžืจื•ืงื• ื ืžืฆืื• ื ื•ืฉืื™ื ืืช ื”ืžื•ื˜ืฆื™ื” ื‘ืขื™ืงืจื• ืœื”ืคืœื•ื˜ื™ืค ื–ื”ื” ื ืจืืชื” ื”ืžื•ื˜ืฆื™ื” ื”ืคืœื•ื˜ื™ืค ื”ืจืงืข ืฉืขืœื™ื• )Genetic drift( ืฉื ืžืฆื ืืฆืœ ืืฉื›ื ื–ื™ื ื•ื ืจืื” ืฉืžื“ื•ื‘ืจ ื‘ื–ืœื™ื’ื” ื’ื ื˜ื™ืช

ืžืื•ื›ืœื•ืกื™ื™ื” ืœืื•ื›ืœื•ืกื™ื™ื”.ื‘ื“ื•ืžื” ืœื›ืš, ืืฆืœ ื“ืจื•ื–ื™ื ื ืžืฆืื” ืžื•ื˜ืฆื™ื” ื™ื—ื™ื“ื” ืืฉืจ ื–ื•ื”ืชื” ื‘ื›ืžื” ื ื™ืชืŸ ื”ื™ื” ื™ื™ืฉื•ื‘ื™ื ืžืจื•ื—ืงื™ื ื–ื” ืžื–ื”, ื•ืœืžืจื•ืช ืžืืžืฆื™ื ืฉื ืขืฉื• ืœื ืœื–ื”ื•ืช ืงืฉืจ ืžืฉืคื—ืชื™ ื‘ื“ื•ืจื•ืช ื”ืื—ืจื•ื ื™ื. ืœื ื•ื›ื— ื”ืฉื›ื™ื—ื•ืช ื”ื™ื—ืกื™ืช ืฉืœ ื”ืžื•ื˜ืฆื™ื”, ื ืจืื” ืฉืžื“ื•ื‘ืจ ื‘ืžื•ื˜ืฆื™ื™ืช ืžื™ื™ืกื“ื™ื. ืชืฆืคื™ืช ืžืขื ื™ื™ื ืช ื•ื™ื™ื—ื•ื“ื™ืช Compound( ืœืขื‘ื•ื“ื” ื–ื• ื”ื™ื ืฉืœ ื—ื•ืœื” ืฉื”ื™ื ื”ื˜ืจื•ื–ื™ื’ื•ื˜ื™ืช ืžื•ืจื›ื‘ืช Biobase( ืœื”ืฉืžื˜ื” ืฉืœ ืืœืœ ืฉืœื. ื‘ื‘ืกื™ืก ื”ื ืชื•ื ื™ื )heterozygoteHGMD( ืœื ืชื•ืืจื” ืžื•ื˜ืฆื™ื” ื›ื–ื•. ืืฆืœ ื ื‘ื“ืง ื ื•ืกืฃ ืžืžื•ืฆื ืžืจื•ืงืื™ ื ืžืฆืื” ื”ืฉืžื˜ื” ืœื›ืื•ืจื” ืฉืœ ืืœืœ ืฉืœื, ืื‘ืœ ื‘ืžืงืจื” ื–ื” ืœื ื ื™ืชืŸ ื”ื™ื” ืœืฉืœื•ืœ

ืื™โ€“ืื‘ื”ื•ืช.ื‘ืื•ื›ืœื•ืกื™ื™ื” ื”ืžื•ืกืœืžื™ืช ื ืžืฆื ืจืคืจื˜ื•ืืจ ืขืฉื™ืจ ืฉืœ ืžื•ื˜ืฆื™ื•ืช, ื›ืœ

ืื—ืช ื™ื™ื—ื•ื“ื™ืช ืœืžืฉืคื—ื” ื ืชื•ื ื”. ืืžื ื ื‘ืžืงืจื™ื ืฉื ืฆืคื• )ืœืžืขื˜ ืื—ื“( ื”ื—ื•ืœื™ื ื ื•ืœื“ื• ืœื”ื•ืจื™ื ืฉื™ืฉ ื‘ื™ื ื™ื”ื ืงืจื‘ืช ื“ื, ืืš ื‘ืฉืชื™ื™ื ืžื”ืžืฉืคื—ื•ืช

ื”ื—ื•ืœื™ื ื”ื ื”ื˜ืจื•ื–ื™ื’ื•ื˜ื™ื ืžื•ืจื›ื‘ื™ื, ื•ื™ืฉ ืœื”ื ืฉืชื™ ืžื•ื˜ืฆื™ื•ืช ืฉื•ื ื•ืช.

ืกื™ื›ื•ืื ืžืฆืื•ืช ื‘ื—ื–ื™ืช ื”ืฉื™ืจื•ืช ื•ื™ืœืกื•ืŸ ืœื–ื™ื”ื•ื™ ื”ืžื•ื˜ืฆื™ื•ืช ื‘ืžื—ืœืช ื‘ื“ื™ืงื•ืช ื”ืงืœื™ื ื™, ื•ื‘ืžืงืจื™ื ืžืกื•ื™ืžื™ื ื”ื‘ื“ื™ืงื” ื™ื›ื•ืœื” ืœื”ื—ืœื™ืฃ ื‘ื“ื™ืงื•ืช ืคื•ืœืฉื ื™ื•ืช, ื‘ืžื™ื•ื—ื“ ื‘ืžืงืจื™ื ืฉื”ืื‘ื—ื ื” ืื™ื ื” ื•ื“ืื™ืช. ื”ื ืชื•ื ื™ื ื”ืืคื™ื“ืžื™ื•ืœื•ื’ื™ื™ื ืฉื”ื•ืฆื’ื• ื™ื›ื•ืœื™ื ืœื ืชื‘ ื•ืœื™ื™ืขืœ ืืช ื”ื‘ื™ืจื•ืจ ื”ื’ื ื˜ื™, ื•ื”ืžื•ื˜ืฆื™ื•ืช ื”ื—ื“ืฉื•ืช

ืฉืชื•ืืจื• ืžืจื—ื™ื‘ื•ืช ืืช ื‘ืกื™ืก ื”ื™ื“ืข ื‘ืžื—ืœื”.

ื‘ื™ื‘ืœื™ื•ื’ืจืคื™ื”1. Frydman M, Bonnรฉ-Tamir B, Farrer LA, Conneally PM, Magazanik

A, Ashbel S, Goldwitch Z. Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1819-21.

2. Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nature Genet. 1993;5: 327-337.

3. Bonnรฉ-Tamir B, Frydman M, Agger MS, Bekeer R, Bowcock AM, Hebert JM, Cavalli-Sforza LL, Farrer LA. Wilson's disease in Israel: a genetic and epidemiological study. Ann Hum Genet. 1990 May;54(Pt 2):155-68.

4. Kalinsky H, Funes A, Zeldin A, Pel-Or Y, Korostishevsky M, Gershoni-Baruch R, Farrer LA, Bonne-Tamir B. Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups. Hum Mutat. 1998;11(2):145-51.

ื‘ื“ื•ืžื” ืœื›ืš, ืืฆืœ ื“ืจื•ื–ื™ื ื ืžืฆืื” ืžื•ื˜ืฆื™ื” ื™ื—ื™ื“ื” ืืฉืจ ื–ื•ื”ืชื” ื‘ื›ืžื” ื™ื™ืฉื•ื‘ื™ื ืžืจื•ื—ืงื™ื ื–ื” ืžื–ื”, ื•ืœืžืจื•ืช ืžืืžืฆื™ื ืฉื ืขืฉื• ืœื ื ื™ืชืŸ ื”ื™ื” ืœื–ื”ื•ืช ืงืฉืจ ืžืฉืคื—ืชื™ ื‘ื“ื•ืจื•ืช ื”ืื—ืจื•ื ื™ื. ืœื ื•ื›ื— ื”ืฉื›ื™ื—ื•ืช ื”ื™ื—ืกื™ืช ืฉืœ ื”ืžื•ื˜ืฆื™ื”, ื ืจืื” ืฉืžื“ื•ื‘ืจ ื‘ืžื•ื˜ืฆื™ื™ืช ืžื™ื™ืกื“ื™ื

ืจื™ืฆื•ืฃ ื”ื’ืŸ ื™ื›ื•ืœ ืœืกื™ื™ืข ื‘ืžืงืจื™ื ืฉื‘ื”ื ื™ืฉ ืœื‘ื˜ื™ื ืœื’ื‘ื™ ื”ืื‘ื—ื ื”, ื‘ืžืงืจื™ื ืฉื‘ื”ื ื“ืจื•ืฉ ื™ื™ืขื•ืฅ ืœืคื ื™ ื ื™ืฉื•ืื™ืŸ ื•ื‘ืžืงืจื™ื ืฉื‘ื”ื ื“ืจื•ืฉื” ืืœื˜ืจื ื˜ื™ื‘ื” ืœื ืคื•ืœืฉื ื™ืช ืœืฆื•ืจืš ืื‘ื—ื•ืŸ. ื ื•ื›ื— ื”ืขื•ื‘ื“ื” ืฉืจื•ื‘ ื”ืžื•ื˜ืฆื™ื•ืช ืžืจื•ื›ื–ื•ืช ื‘ึพ11 ืืงืกื•ื ื™ื ื•ื‘ืงื‘ื•ืฆื•ืช ืืชื ื™ื•ืช ืžื•ื’ื“ืจื•ืช, ืื•ืคื™ื™ืŸ ืจืคืจื˜ื•ืืจ ืฉืœ ืžื•ื˜ืฆื™ื•ืช ืฉื›ื™ื—ื•ืช, ื•ื”ื‘ื“ื™ืงื” ืžื•ืฆืขืช ื‘ื›ืžื” ืžืชืืจื™ื, ื›ื“ื™ ืœื ืกื•ืช ื•ืœืฆืžืฆื ืขืœื•ื™ื•ืช. ื‘ืฉืœื‘ ืจืืฉื•ืŸ ื ื‘ื“ืง ืžืกืคืจ ืงื˜ืŸ ืฉืœ ืžื•ื˜ืฆื™ื•ืช ื”ืžื•ื›ืจื•ืช ื‘ืงื‘ื•ืฆื” ื”ืืชื ื™ืช ืฉืืœื™ื” ืžืฉืชื™ื™ืš ื”ื ื‘ื“ืง. ืื ื”ื‘ื“ื™ืงื” ืœื ืžื’ืœื” ืคื’ื, ื ื‘ื“ืงื™ื 11 ื”ืืงืกื•ื ื™ื ืฉื‘ื”ื ืžืจื•ื›ื–ื•ืช ืจื•ื‘ ื”ืžื•ื˜ืฆื™ื•ืช. ืจืง ืื ื‘ืฉื ื™ ื”ืฉืœื‘ื™ื ื”ืจืืฉื•ื ื™ื ืœื

ืžืชื’ืœื” ืคื’ื, ื ื‘ื“ืงื™ื 10 ื”ืืงืกื•ื ื™ื ื”ื ื•ืชืจื™ื.

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”

DNA. ืชื•ืืจื• ื’ื ื”ืฉืžื˜ื•ืช ื”ืฉืžื˜ื•ืช ืงื˜ื ื•ืช ืื• ื”ื—ื“ืจื•ืช ืฉืœ ืจืฆืคื™ ื’ื“ื•ืœื•ืช, ืื‘ืœ ื‘ื‘ืกื™ืก ื”ื ืชื•ื ื™ื ื”ืฆื™ื‘ื•ืจื™ ืœื ืชื•ืืจื• ื”ืฉืžื˜ื•ืช ืฉืœ ืืงืกื•ืŸ ืฉืœื ื•ื’ื ืœื ืฉืœ ืืœืœ ืฉืœื, ื•ืืคืฉืจ ืฉื”ื“ื‘ืจ ื ื•ื‘ืข ืžืžื’ื‘ืœื•ืช ืฉื™ื˜ืช ื–ื™ื”ื•ื™ ื”ืžื•ื˜ืฆื™ื•ืช. ื‘ื”ืงืฉืจ ื–ื” ืžืขื ื™ืŸ ืœืฆื™ื™ืŸ ื›ื™ ื‘ื›โ€“17% ืžื”ืžืงืจื™ื ื”ืื•ืคื™ื ื™ื™ื ืฉืœ

ืžื—ืœืช ื•ื™ืœืกื•ืŸ ืœื ื ืžืฆืื” ืžื•ื˜ืฆื™ื” ื‘ืฉื™ื˜ื•ืช ืกื˜ื ื“ืจื˜ื™ื•ืช1. ืืคื™ื“ืžื™ื•ืœื•ื’ื™ื”: ืžื—ืœืช ื•ื™ืœืกื•ืŸ ืžื•ืคื™ืขื” ื‘ื›ืœ ื”ืงื‘ื•ืฆื•ืช ื”ืืชื ื™ื•ืช, ืืš ืฉื›ื™ื—ื•ืช ื”ืžื—ืœื” ืฉื•ื ื” ื‘ืื•ื›ืœื•ืกื™ื•ืช ืฉื•ื ื•ืช. ื‘ืื•ื›ืœื•ืกื™ื•ืช ืฉื‘ื”ืŸ ื™ืฉ ืจื™ื‘ื•ื™ ื™ื•ืชืจ. ื‘ืื•ื›ืœื•ืกื™ื•ืช ืฉื‘ื”ืŸ ื”ื ื™ืฉื•ืื™ืŸ ื ื™ืฉื•ืื™ ืงืจื•ื‘ื™ื ื”ืžื—ืœื” ืฉื›ื™ื—ื” ื”ื ืืงืจืื™ื™ื, ืฉื›ื™ื—ื•ืช ื”ืžื—ืœื” ื”ื™ื ื›โ€“1/30,000 ื•ืฉื›ื™ื—ื•ืช ื”ื ืฉืื™ื

ืžื•ืขืจื›ืช ื‘โ€“1/90. ื”ืฉื›ื™ื—ื•ืช ืฉืœ ืžื—ืœืช ื•ื™ืœืกื•ืŸ ื‘ื™ืฉืจืืœ ืื™ื ื” ื™ื“ื•ืขื” ื‘ื•ื•ื“ืื•ืช. ื‘ืขื‘ื•ื“ืชื ื™ืฉืจืืœื™ื•ืช 51 ืžืฉืคื—ื•ืช ืขืœ ื ืืกืฃ ืžื™ื“ืข ื•ืขืžื™ืชื™ื” ื‘ื•ื ื”โ€“ืชืžื™ืจ ืฉืœ

ืฉืื•ื‘ื—ื ื• ื‘ืฉื ื™ื 1989-1959. ื”ืฉื›ื™ื—ื•ืช ืฉื—ื•ืฉื‘ื” ื‘ืงืจื‘ ื™ื”ื•ื“ื™ื ืžืžื•ืฆื ืืฉื›ื ื–ื™ )10 ืžืฉืคื—ื•ืช( ื•ืฆืคื•ืŸ ืืคืจื™ืงืื™ )5 ืžืฉืคื—ื•ืช( ื”ื™ื™ืชื” 1/40,000, ื‘ืงืจื‘ ื™ื”ื•ื“ื™ื ืžืžื•ืฆื 6( ื™ื”ื•ื“ื™ื ืžืžื•ืฆื ืชื™ืžื ื™ 1:25,000, ื‘ืงืจื‘ )5 ืžืฉืคื—ื•ืช( ืขื™ืจืืงื™ ืžืฉืคื—ื•ืช( 1:9,000 ื•ื‘ืงืจื‘ ื™ื”ื•ื“ื™ื ืžืžื•ืฆื ืคืจืกื™ ื•ื‘ื•ื›ืจื™ )11 ืžืฉืคื—ื•ืช( 1:4,000. ื”ืฉื›ื™ื—ื•ืช ื‘ืงืจื‘ ืžื•ืกืœืžื™ื )8 ืžืฉืคื—ื•ืช( ื”ื™ื™ืชื” 1:10,000

ื•ื‘ืงืจื‘ ื“ืจื•ื–ื™ื )5 ืžืฉืคื—ื•ืช( 1:3,000. ืœื ื•ื›ื— ื”ืฉื™ืขื•ืจ ื”ื’ื‘ื•ื” ืฉืœ ื ื™ืฉื•ืื™ ืงืจื•ื‘ื™ื ื‘ืงืจื‘ ื”ืžื•ืกืœืžื™ื, ื”ื“ืจื•ื–ื™ื ื ื™ืกื™ื•ืŸ ืœื—ืฉื‘ ืืช ืฉื›ื™ื—ื•ืช ื”ื’ืŸ ืชื•ืš ื™ื”ื•ื“ื™ื•ืช ืžืกื•ื™ืžื•ืช, ื ืขืฉื” ื•ืขื“ื•ืช ื”ืชื—ืฉื‘ื•ืช ื‘ืžืงื“ื ื”ืงืจื‘ื” )Coeficient of inbreeding( ื•ื‘ื”ื ื—ื” ืฉืจืง 90% ืžื”ืžืงืจื™ื ืื•ืชืจื•. ื‘ื—ื™ืฉื•ื‘ ื›ื–ื” ื ืžืฆื ื›ื™ ืฉื›ื™ื—ื•ืช ื”ื ืฉืื™ื ื‘ืงืจื‘ ืืฉื›ื ื–ื™ื ื•ืžื•ืกืœืžื™ื ืขื•ืžื“ืช ืขืœ 1/106 ื•โ€“1/108 ื‘ื”ืชืืžื”, ื‘ืงืจื‘ ื™ื•ืฆืื™ ืื™ืจืืŸ ื•ื“ืจื•ื–ื™ื ืขืœ 1/46 ื•โ€“1/47 ื‘ื”ืชืืžื”, ื‘ืงืจื‘ ืชื™ืžื ื™ื ืขืœ 1/65, ื‘ืงืจื‘ ื™ื•ืฆืื™ ืฆืคื•ืŸ ืืคืจื™ืงื” ืขืœ 1/172 ื•ื‘ืงืจื‘ ื™ื•ืฆืื™ ืขื™ืจืืง ืขืœ 1/192. ืœื•ื•ื“ืื™ ืฉื”ืžืกืคืจื™ื ื•ืงืจื•ื‘ ืืœื• ื‘ื”ืกืชื™ื™ื’ื•ืช, ืœื ืชื•ื ื™ื ื™ืฉ ืœื”ืชื™ื™ื—ืก

ื”ืืžื™ืชื™ื™ื ื’ื‘ื•ื”ื™ื ื™ื•ืชืจ. ืจืคืจื˜ื•ืืจ ื”ืžื•ื˜ืฆื™ื•ืช: ื”ืžื•ื˜ืฆื™ื•ืช ืฉืชื•ืืจื• ื‘ื’ืŸ ืื™ื ืŸ ืžืคื•ื–ืจื•ืช ื‘ืื•ืคืŸ ื”ื™ื ื‘ื™ื•ืชืจ ื”ืฉื›ื™ื—ื” ื”ืžื•ื˜ืฆื™ื” ื”ืื™ืจื•ืคืื™ืช, ื•ื‘ืื•ื›ืœื•ืกื™ื™ื” ืืงืจืื™, ื”ื—ืœืคื” ืฉืœ ื—ื•ืžืฆืช ื”ืืžื™ื ื• ื”ื™ืกื˜ื™ื“ื™ืŸ ื‘ืขืžื“ื” 1069 ืฉืœ WNP ื‘ื’ืœื•ื˜ืžื™ืŸ )H1069Q(. ืžื•ื˜ืฆื™ื” ื–ื• ืœื‘ื“ื” ืžื”ื•ื•ื” ื›โ€“35%-45% ืžื›ืœืœ ื”ืžื•ื˜ืฆื™ื•ืช. ื‘ืื•ื›ืœื•ืกื™ื™ื” ืžืžื•ืฆื ืื•ืจื™ื™ื ื˜ืœื™ ืฉื›ื™ื—ื” ื™ื—ืกื™ืช ื”ืžื•ื˜ืฆื™ื” R778L ื”ืžื”ื•ื•ื”

57% ืžื›ืœืœ ื”ืžื•ื˜ืฆื™ื•ืช. ื›โ€“80% ืžื”ืžื•ื˜ืฆื™ื•ืช ื‘ื’ืŸ ื ืžืฆืื•ืช ื‘โ€“10 ืžืชื•ืš 21 ื”ืืงืกื•ื ื™ื )ืืงืกื•ื ื™ื 8, 10, 11, 12, 13, 14, 17, 18, 19 ื•โ€“20( ื•ืžื™ืงื•ืžืŸ ืžืขื™ื“ ืขืœ ื”ื—ืฉื™ื‘ื•ืช ื”ืคื•ื ืงืฆื™ื•ื ืœื™ืช ืฉืœ ืืงืกื•ื ื™ื ืืœื•. ื ื•ืกืฃ ืœื›ืš, ื‘ืงืจื‘ ื™ื”ื•ื“ื™ื ืžืžื•ืฆื ืืฉื›ื ื–ื™ ืฉื›ื™ื—ื” ื™ื—ืกื™ืช ืžื•ื˜ืฆื™ื” ื‘ืืงืกื•ืŸ M645R( 6( ื•ื™ื™ืชื›ืŸ ืฉื”ื™ื ืžื™ื™ืฆื’ืช ืžื•ื˜ืฆื™ื™ืช

.)Founder mutation( ืžื™ื™ืกื“ื™ืื‘ืฉื ืช 1998 ืชื™ืืจื• ืงืœื™ื ืกืงื™ ื•ืขืžื™ืชื™ื” ืžื•ื˜ืฆื™ื•ืช ืฉื ืžืฆืื• ืืฆืœ ื—ื•ืœื™ื

ื‘ื™ืฉืจืืœ ื•ืกื™ื•ื•ื’ื• ืื•ืชืŸ ืœืคื™ ื”ืžื•ืฆื ื”ืขื“ืชื™ ืฉืœ ื”ื—ื•ืœื™ื. ื ื•ืกืฃ ืœืžืคื•ืจื˜ ืœืขื™ืœ, ืงืœื™ื ืกืงื™ ื•ืขืžื™ืชื™ื” ]4[ ืชื™ืืจื• ืขื•ื“ 4 ืžื•ื˜ืฆื™ื•ืช G1213V ,ืืฆืœ ื™ื•ืฆืื™ ืœื•ื‘/ื˜ื•ื ื™ืก W969Q ,ืืฆืœ ืชื™ืžื ื™ื D765B :ื›ื“ืœืงืžืŸ

ืืฆืœ ื—ื•ืœื” ืžื›ื•ืจื“ื™ืกื˜ืŸ ื•โ€“1639delC ืืฆืœ ืžื•ืกืœืžื™ื.ื‘ืฉื ืช 2007 ื”ื—ืœ ื”ืžื›ื•ืŸ ื”ื’ื ื˜ื™ ื‘ื‘ื™"ื— ืฉื™ื‘ื ืœื‘ืฆืข ืจื™ืฆื•ืฃ ืฉืœ ื”ื’ืŸ ืœืžื—ืœืช ื•ื™ืœืกื•ืŸ. ืจื™ืฆื•ืฃ ื”ื’ืŸ ื™ื›ื•ืœ ืœืกื™ื™ืข ื‘ืžืงืจื™ื ืฉื‘ื”ื ื™ืฉ ืœื‘ื˜ื™ื ืœื’ื‘ื™ ื”ืื‘ื—ื ื”, ื‘ืžืงืจื™ื ืฉื‘ื”ื ื“ืจื•ืฉ ื™ื™ืขื•ืฅ ืœืคื ื™ ื ื™ืฉื•ืื™ืŸ ื•ื‘ืžืงืจื™ื ืฉื‘ื”ื ื“ืจื•ืฉื” ืืœื˜ืจื ื˜ื™ื‘ื” ืœื ืคื•ืœืฉื ื™ืช ืœืฆื•ืจืš ืื‘ื—ื•ืŸ. ื ื•ื›ื— ื”ืขื•ื‘ื“ื” ืฉืจื•ื‘ ื”ืžื•ื˜ืฆื™ื•ืช ืžืจื•ื›ื–ื•ืช ื‘โ€“11 ืืงืกื•ื ื™ื ื•ื‘ืงื‘ื•ืฆื•ืช ืืชื ื™ื•ืช ืžื•ื’ื“ืจื•ืช, ืื•ืคื™ื™ืŸ ืจืคืจื˜ื•ืืจ ืฉืœ ืžื•ื˜ืฆื™ื•ืช ืฉื›ื™ื—ื•ืช, ื•ื”ื‘ื“ื™ืงื” ืžื•ืฆืขืช ื‘ื›ืžื” ืžืชืืจื™ื,

1ื”ืžื•ื˜ืฆื™ื•ืช ืฉืชื•ืืจื• ืžืจื•ื›ื–ื•ืช ื‘ืืชืจ:

http://www.hgmd.cf.ac.uk/ac/gene.php?-gene=ATP7B

ื›ื“ื™ ืœื ืกื•ืช ื•ืœืฆืžืฆื ืขืœื•ื™ื•ืช. ื‘ืฉืœื‘ ืจืืฉื•ืŸ ืžื•ืฆืข ืœื‘ื“ื•ืง ืžืกืคืจ ืงื˜ืŸ ืฉืœ ืžื•ื˜ืฆื™ื•ืช ื”ืžื•ื›ืจื•ืช ื‘ืงื‘ื•ืฆื” ื”ืืชื ื™ืช ืฉืืœื™ื” ืžืฉืชื™ื™ืš ื”ื ื‘ื“ืง. ืื ื”ื‘ื“ื™ืงื” ืœื ืžื’ืœื” ืคื’ื, ื ื‘ื“ืงื™ื 11 ื”ืืงืกื•ื ื™ื ืฉื‘ื”ื ืžืจื•ื›ื–ื•ืช ืจื•ื‘ ื”ืžื•ื˜ืฆื™ื•ืช. ืจืง ืื ืฉื ื™ ื”ืฉืœื‘ื™ื ื”ืจืืฉื•ื ื™ื ืžืขืœื™ื ื—ืจืก, ื ื‘ื“ืงื™ื 10

ื”ืืงืกื•ื ื™ื ื”ื ื•ืชืจื™ื. ,V1286F ื•โ€“ L568R ,IVS6-19T>A ,M885I ,W939C ื”ืžื•ื˜ืฆื™ื•ืช ื”ืžื“ื•ื•ื—ื•ืช ืœืจืืฉื•ื ื”, ื”ืŸ ืžื•ื˜ืฆื™ื•ืช ืฉืœื ื ื›ืœืœื•ืช ื‘ืžืื’ืจ ื”ื ืชื•ื ื™ื ื”ืฆื™ื‘ื•ืจื™ ื•ืœื ืชื•ืืจื• ื‘ืขื‘ืจ. ื”ืžื•ื˜ืฆื™ื” IVS6-19T>A ื”ื™ื ืžืขื ื™ื™ื ืช ื‘ืžื™ื•ื—ื“ ืžื›ื™ื•ื•ืŸ ืฉื”ื™ื ื ืžืฆืืช 19 ื‘ืกื™ืกื™ื ืœืคื ื™ ื ืงื•ื“ืช ื”ืฉื—ื‘ื•ืจ ืฉืœ ืืงืกื•ืŸ 7, ื•ื‘ืžืื’ืจ ื”ื ืชื•ื ื™ื ืœื ืชื•ืืจื” ืžื•ื˜ืฆื™ื” ื”ื ืžืฆืืช ื›ื” ืขืžื•ืง ื‘ืชื•ืš ื”ืื™ื ื˜ืจื•ืŸ, ืืš ื™ื•ืฆืจืช ืจืฆืฃ AG )ื‘ืžืงื•ื TG( ืฉื”ื•ื ื ืงื•ื“ืช ืฉื—ื‘ื•ืจ ืฉื’ื•ื™ื” ืฉื™ื›ื•ืœื” ืœื”ื•ืกื™ืฃ

19 ื‘ืกื™ืกื™ื ืœืืงืกื•ืŸ 7.ืžื”ืชื•ืฆืื•ืช ืขื•ืœื” ื›ื™ ื‘ื“ื™ืงืช ืฉืœื•ืฉ ืžื•ื˜ืฆื™ื•ืช ื‘ืงืจื‘ ื™ื”ื•ื“ื™ื ืžืžื•ืฆื

ื•ืŸืก

ื™ืœืช ื•

ื—ืœืž

CommentsEthnic origin

Patient number*

Allele numberExon

Missense Mutation

NewMoslem124L568R

Ashkenazi666M645R#

NewAshkenazi117M885I

NewMoslem1212W939C

Moslem2413A1003T

Ashkenazi3314E1064A#

Ashkenazi131714H1069Q#

Morocco2314H1069Q#

Iran1117R1151C

NewMoslem1117I1184T+

Ashkenazi1217H1207R

Iran2217T1220M

Bokhara1218V1262F

Ashkenazi1118G1281D

NewBokhara1118V1286F

Ashkenazi, Bokhara, Iran

33Unknown

CommentsEthnic origin

Patient number*

Allele numberExon

Nonsense Mutation

Iran122c.846delT#

Iran?112c.1445delT

Moslem222-3IVS2+5GT

NewMoslem226-7IVS6-19T>T-A

Druze5917c.3648del6bp#

NewDruze11Allel Deletion

Non paternity not excluded

Morocco11Allel Deletion

52*68Total

ื˜ื‘ืœื” ืžืก' 1. ืคื™ืจื•ื˜ ื”ืžื•ื˜ืฆื™ื•ืช ืฉื ืžืฆืื• ืืฆืœ 34 ื—ื•ืœื™ื ื ื•ืกืคื™ื:

*ื—ื•ืœื™ื ืฉื ืžืฆืื• ืืฆืœื ืฉืชื™ ืžื•ื˜ืฆื™ื•ืช ืฉื•ื ื•ืช ื ืกืคืจื• ืคืขืžื™ื™ื. # ืžื•ื˜ืฆื™ื•ืช ืฉืชื•ืืจื• ื‘ืืจืฅ ืขืœึพื™ื“ื™ ืงืœื™ื ืกืงื™ ื•ื—ื‘' ื‘ืฉื ืช 1998 ]4[

+ ื”ืžื•ื˜ืฆื™ื” ื”ืฉื ื™ื™ื” ืฉืœ ื—ื•ืœื” ื–ื• 1369delC ื–ื•ื”ืชื” ืข"ื™ ืงืœื™ื ืกืงื™ ื•ื—ื‘' ]4[.

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ืงืจืืช ืฆืืช ื”ื”ื ื—ื™ื•ืช ื”ืงืœื™ื ื™ื•ืช ื”ืื™ืจื•ืคืื™ื•ืช ืœื˜ื™ืคื•ืœ ื‘ืžื—ืœืช ืœืชื•ืš ื”ืชื™ื™ื—ืกื•ืช ื”ื’ื ื˜ื™ ื‘ื ื•ืฉื ืขื“ื›ื•ืŸ ืื ื• ืžื‘ื™ืื™ื ื•ื™ืœืกื•ืŸ,

ืœื”ืฉืœื›ื•ืช ื™ื™ื—ื•ื“ื™ื•ืช ืœืืจืฅ.ื ื—ื•ืฉืช ื”ื™ื ื™ืกื•ื“ ืงื•ืจื˜ ื—ื™ื•ื ื™ ื”ื“ืจื•ืฉ ืœืคืขื™ืœื•ืช ืื ื–ื™ืžื™ื ื•ืžืขืจื›ื•ืช ื‘ืงืจื” ืžื•ืœืงื•ืœืจื™ืช ืฉื•ื ื•ืช, ืขืงื‘ ื”ื™ื›ื•ืœืช ืฉืœ ื”ืื˜ื•ื ืœืขื‘ื•ืจ ื‘ืงืœื•ืช ืžืžืฆื‘ ืžื—ื•ืžืฆืŸ ืœืžืฆื‘ ืžื—ื•ื–ืจ ื•ืœื”ืคืš. ืื•ืชื” ื™ื›ื•ืœืช ื”ืžืงื ื” ืœื ื—ื•ืฉืช ืืช ื—ืฉื™ื‘ื•ืชื” ื”ื‘ื™ื•ืœื•ื’ื™ืช, ืขืœื•ืœื” ืœื’ืจื•ื ืœืคื’ื™ืขื” ื›ืืฉืจ ื”ื ื—ื•ืฉืช ืžืฆื˜ื‘ืจืช ื‘ืขื•ื“ืฃ ื•ื›ืืฉืจ ื”ื™ื ื—ืกืจื” ืžืกื™ื‘ื•ืช ืžื˜ื‘ื•ืœื™ื•ืช ืื• ืื—ืจื•ืช. ืžื—ืœืช ื•ื™ืœืกื•ืŸ )WD( ื”ื™ื ืžื—ืœื” ืฉื‘ื” ื ื—ื•ืฉืช ื ืื’ืจืช ื•ื’ื•ืจืžืช ืœื ื–ืง ืžืฆื˜ื‘ืจ ืœืื™ื‘ืจื™ ื‘ืชื•ืจืฉื” ืžื•ืขื‘ืจืช ื”ืžื—ืœื” ื•ื”ื›ืœื™ื•ืช. ื”ืžื•ื— ื”ื›ื‘ื“, ื•ื‘ื”ื ืžื˜ืจื” ืื•ื˜ื•ื–ื•ืžื™ืช ืจืฆืกื™ื‘ื™ืช ื•ื‘ืžืจื‘ื™ืช ื”ืžืงืจื™ื ื ื™ืชืŸ ืœืžืฆื•ื ืืฆืœ ื”ืœื•ืงื™ื ื‘ื”

.ATP7B ืคื’ื ื‘ื’ืŸื ื™ืชืŸ ืœืžืฆื•ื ืฉื•ื ื•ืช ืงืœื™ื ื™ืช ื ื™ื›ืจืช ื‘ื™ืŸ ื”ื—ื•ืœื™ื ื‘ืžื—ืœื”, ื•ืืคื™ืœื• ื‘ื™ืŸ ื—ื•ืœื™ื ื‘ืื•ืชื” ืžืฉืคื—ื” ืขืฆืžื”. ื—ืœืง ืžื”ืฉื•ื ื•ืช ืงืฉื•ืจ ื‘ืกื•ื’ ื”ืžื•ื˜ืฆื™ื”, ืื‘ืœ ื‘ืžืงืจื™ื ืจื‘ื™ื ื”ืกื™ื‘ื” ืœืฉื•ื ื•ืช ื”ืงืœื™ื ื™ืช ืื™ื ื” ื™ื“ื•ืขื”, ื•ืžื™ื•ื—ืกืช ืœื”ืฉืคืขืชื ืฉืœ ื’ื ื™ื ืžืžืชื ื™ื )Modifier genes( ืื• ืฉืœ ื’ื•ืจืžื™ ืกื‘ื™ื‘ื”

ื•ืื•ืจื— ื—ื™ื™ื. ื‘ื–ืจื•ืข ื”ืืจื•ื›ื” ืฉืœ 14.1 1985 ืœืคืก ื”ื’ืŸ ืœืžื—ืœื” ืžื•ืคื” ื‘ืฉื ืช ื›ืจื•ืžื•ื–ื•ื 13 ]1[. ื‘ืฉื ืช 1993 ื”ื’ืŸ ืฉื•ื‘ื˜, ื•ื ืžืฆื ืฉื”ื•ื ื—ืœื‘ื•ืŸ ื˜ืจื ืกืคื•ืจื˜ ื˜ืจื ืกืžืžื‘ืจื ืœื™ ื‘ืขืœ ืืชืจ ืคืขื™ืœ ื”ืงื•ืฉืจ ATP, ื•ืฉื™ื™ืš ืœืžืฉืคื—ืช ื—ืœื‘ื•ื ื™ื ื”ื ืงืจืื™ื P - type ATPase ื•ื—ื•ืœืงื™ื ื“ืžื™ื•ืŸ ืžื‘ื ื™ ]2[. ื‘ื”ืžืฉืš ื ืžืฆื ืฉื”ื’ืŸ ื”ื•ื ื‘ืขืœ 21 ืืงืกื•ื ื™ื ื•ืžืงื•ื“ื“ ื—ืœื‘ื•ืŸ ืฉืœ 1,465 ื—ื•ืžืฆื•ืช ืืžื™ื ื• ืฉื ืงืจื ื•ื™ืฉ ืœื• ืฉื ื™ ืชืคืงื™ื“ื™ื WDP. ื”ื—ืœื‘ื•ืŸ ืžืขื‘ื™ืจ ื ื—ื•ืฉืช ื“ืจืš ืงืจื•ื ื”ืชื ืขื™ืงืจื™ื™ื: ืžืกื™ืจืช ื ื—ื•ืฉืช ืœืฆืจื•ืœื•ืคืœื–ืžื™ืŸ ื•ื”ืคืจืฉืช ืขื•ื“ืคื™ ื ื—ื•ืฉืช ืžืชืื™

ื”ื›ื‘ื“ ืืœ ื”ืžืจื”. ืžื‘ื—ื™ื ื” ืžื‘ื ื™ืช, ืœื—ืœื‘ื•ืŸ ื›ืžื” ืืชืจื™ื ืชืคืงื•ื“ื™ื™ื )Domains(, ื”ืฉืžื•ืจื™ื ืžื‘ื—ื™ื ื” ืื‘ื•ืœื•ืฆื™ื•ื ื™ืช: ื‘ืงืฆื” ื”ืืžื™ื ื™ ืฉืœ ื”ืžื•ืœืงื•ืœื” ื™ืฉ 6 ืืชืจื™ ืงืฉื™ืจื” ืฉืœ ื ื—ื•ืฉืช, ื”ื ืžืฆืื™ื ื‘ืชื•ืš ื”ืฆื™ื˜ื•ื–ื•ืœ. ืฉืžื•ื ื” ืืชืจื™ื ื”ื™ื“ืจื•ืคื•ื‘ื™ื™ื ื—ื•ื“ืจื™ื ื‘ื™ืŸ ื”ืืชืจ ื•ื“ืจื›ื ืžืชื‘ืฆืขืช ื”ืขื‘ืจืช ื”ื ื—ื•ืฉืช. ืืช ืžืžื‘ืจื ืช ื”ืชื ื”ื”ื™ื“ืจื•ืคื•ื‘ื™ ื”ืจื‘ื™ืขื™ ืœื—ืžื™ืฉื™ ื ืžืฆื ืืชืจ ืฉืžื•ืจ )A(, ื•ื‘ื™ืŸ ื”ืžืขื‘ืจ ื”ืฉื™ืฉื™ ืœืฉื‘ื™ืขื™ ื ืžืฆื ืืชืจ ื”ื–ื™ืจื—ื•ืŸ )ืคื•ืกืคื•ืจื™ืœืฆื™ื”( )P( ื•ืื—ืจื™ื• ืืชืจ ื”ืงื™ืฉื•ืจ ืฉืœ ืžื•ืœืงื•ืœืช N( ATP(, ื”ืžืกืคืงืช ืืช ื”ืื ืจื’ื™ื” ื”ื“ืจื•ืฉื” ืœืชืคืงื•ื“ ื”ืชืขืœื” ืฉื“ืจื›ื” ืžื•ืขื‘ืจื™ื ืงื˜ื™ื•ื ื™ ื”ื ื—ื•ืฉืช ืืœ ืžื—ื•ืฅ ืœืชื. ื‘ืืชืจ ื”ื–ื™ืจื—ื•ืŸ ื ืžืฆื ืžื•ื˜ื™ื‘ ืงื‘ื•ืข ืฉืœ 5 ื—ื•ืžืฆื•ืช ืืžื™ื ื• Asp-Lys-Thr-Gly-Thr ื”ืžืฉื•ืชืฃ ืœื›ืœ ื”ื—ืœื‘ื•ื ื™ื ืžืกื•ื’ P - type ATPase . ื”ื—ื•ืžืฆื” ื”ืืกืคืจื˜ื™ืช ื‘ืžื•ื˜ื™ื‘ ื–ื” ืขื•ื‘ืจืช ื–ื™ืจื—ื•ืŸ ื‘ื–ืžืŸ ืžื—ื–ื•ืจ ื”ืขื‘ืจืช ื”ืงื˜ื™ื•ืŸ. ื”ืงืฆื” ื”ืงืจื‘ื•ืงืกื™ืœื™ ืฉืœ

ื”ืžื•ืœืงื•ืœื” ื˜ื•ื‘ืœ ื’ื ื”ื•ื ื‘ืชื•ืš ื”ืฆื™ื˜ื•ื–ื•ืœ. ืžื—ืงืจื™ื ื‘ื—ื™ื™ื“ืงื™ื ื•ื‘ื‘ืขืœื™ ื—ื™ื™ื ื”ืจืื• ื›ื™ ืจื•ื‘ ื”ื ื—ื•ืฉืช ื ืกืคื’ืช ื‘ืงื™ื‘ื” SLC31A1 ื•ื‘ืชืจื™ืกืจื™ื•ืŸ, ื•ื‘ืชื”ืœื™ืš ืžืฉืชืชืฃ ื—ืœื‘ื•ืŸ ื”ืžืงื•ื“ื“ ืขืœโ€“ื™ื“ื™ ื”ื’ืŸืœื”ืชืคืชื— ื”ืคืกื™ืงื• ืœื’ืŸ ืžื•ื˜ืฆื™ื” ืœื”ื ืฉื”ื•ื—ื“ืจื” ืขื›ื‘ืจื™ื .)CTR1(ื‘ื™ื•ื ื”ืชืฉื™ืขื™ ืœื”ื™ืจื™ื•ืŸ. ื’ืŸ ื—ืฉื•ื‘ ื ื•ืกืฃ ื”ืžืขื•ืจื‘ ื‘ืกืคื™ื’ืช ื”ื ื—ื•ืฉืช ื‘ืžืขื™ ื•ื‘ื”ืขื‘ืจืชื” ืœืื ื–ื™ืžื™โ€“ืžื˜ืจื” ื”ื•ื ื”ื’ืŸ ATP7A, ืฉื—ืกืจ ืฉืœื• ื’ื•ืจื ืœืžื—ืœืช

Menkes ืขืœ ืฆื•ืจื•ืชื™ื” ื”ืฉื•ื ื•ืช.WDP ื‘ืืžืฆืขื•ืช ื—ืœื‘ื•ืŸ ื”ืžืงื•ื“ื“ ืขืœโ€“ื™ื“ื™ ื”ื ื—ื•ืฉืช ืžื•ืขื‘ืจืช ืœื—ืœื‘ื•ืŸ ื”ื’ืŸ ATOX1. ื—ืœื‘ื•ืŸ ื–ื” ืฉื™ื™ืš ืœืžืฉืคื—ืช ื”โ€“Metallochaperons. ืขื›ื‘ืจื™ื ืฉื ื’ืจืžื” ืœื”ื ืžื•ื˜ืฆื™ื” ื‘ื’ืŸ ื–ื” ืžืชื• ื–ืžืŸ ืงืฆืจ ืœืื—ืจ ื”ืœื™ื“ื”. ื‘ืงืจื‘ ื‘ื ื™ ืื“ื ืœื ืชื•ืืจื• ืžื•ื˜ืฆื™ื•ืช ื‘ื’ืŸ ื–ื”, ืื•ืœื ื—ื•ืœื™ื ื‘ืžื—ืœืช ื•ื™ืœืกื•ืŸ ืฉื ืžืฆื ืืฆืœื ื—ืกืจ ืชืคืงื•ื“ื™ ืžืœื ืฉืœ ื”ื’ืŸ ATP7B ื•ืžื—ืกื•ืจ ืžื•ื—ืœื˜ ืฉืœ WDP, ืžืคืชื—ื™ื ืกื™ืžื ื™ ืžื—ืœืช ื•ื™ืœืกื•ืŸ ืจืง ืœืื—ืจ ื›ืžื” ืฉื ื™ื. ืขื•ื‘ื“ื” ื–ื• ืžืขื™ื“ื” ื›ื™ ื™ืฉ ืืฆืœ ื‘ื ื™

ืื“ื ื“ืจื›ื™ื ืืœื˜ืจื ื˜ื™ื‘ื™ื•ืช ืœื”ืขื‘ืจืช ื ื—ื•ืฉืช ืœืื ื–ื™ืžื™ื ื”ืฉื•ื ื™ื. ื ื•ืจืžืœื™ ื’ื•ืœื’'ื™. ื‘ืื•ืคืŸ WDP ืžืžื•ืงื ื‘ืฆื™ื˜ื•ื–ื•ืœ ื‘ืžืขืจื›ืช ื”ื—ืœื‘ื•ืŸ ื•ืฉื ื”ื™ื ื”ื ื—ื•ืฉืช ืžืฉืชื—ืจืจืช ืœืชื•ืš ืžืขืจื›ืช ื”ื”ืคืจืฉื” ืฉืœ ื”ืชื ื ืงืฉืจืช ืœืฆืจื•ืœื•ืคืœื–ืžื™ืŸ ื•ืœื—ืœื‘ื•ื ื™ื ื•ืื ื–ื™ืžื™ื ืื—ืจื™ื ื”ืžื›ื™ืœื™ื ื ื—ื•ืฉืช. ื›ืืฉืจ ืจืžื•ืช ื”ื ื—ื•ืฉืช ื‘ืชื ืžืกื•ื™ื, ืœืกืฃ ืžืขืœ ืขื•ืœื•ืช WDP ืขื•ื–ื‘ ืืช ืžืขืจื›ืช ื’ื•ืœื’'ื™ ืœื–ืขื™ืจโ€“ืฉืœืคื•ื—ื™ื•ืช ื•ืžื•ืขื‘ืจ )ื•ื–ื™ืงื•ืœื•ืช( ื”ื ืžืฆืื•ืช ื‘ืกืžื•ืš ืœืฆื•ืจืš ื”ืชื ืœืžืžื‘ืจื ืช ื”ืžืจื”. ืœืฆื™ื ื•ืจื™ื•ืช ื”ืคืจืฉื” ืœืžืจื” ื”ืžื•ืคืจืฉืช ื”ื ื—ื•ืฉืช ื ืงืฉืจืช ืœื—ืœื‘ื•ื ื™ื ื”ืžื•ื ืขื™ื ืืช ืกืคื™ื’ืชื” ื”ื—ื•ื–ืจืช ื‘ืžืขื™. ื”ื’ืŸ ATP7B ืžื•ื•ืกืช ืืช ื™ืฆื™ืจืช ื”ืฆืจื•ืœื•ืคืœื–ืžื™ืŸ, ื•ืœื›ืŸ ืืฆืœ ื—ื•ืœื™ ื•ื™ืœืกื•ืŸ ืจืžื•ืช ื”ืื ื–ื™ื ื ืžื•ื›ื•ืช. ืœ ื‘ื™ ื›ืžื• ื“ื• ืœืชืคืงื™ ื ื•ืกืฃ ื™ืฉ ืœืฆืจื•ืœื•ืคืœื–ืžื™ืŸ ื ื—ื•ืฉืช, ืคืจื•ืื•ืงืกื™ื“ื–, ืฉืœ ืชืคืงื™ื“ ื•ื‘ืงืจื‘ ื—ื•ืœื™ื ืฉืœื ื ืžืฆื ืืฆืœื ื›ืœืœ ืฆืจื•ืœื•ืคืœื–ืžื™ืŸ, ืžืชืคืชื—ืช ืžื—ืœื” ื ื•ื™ืจื•ืœื•ื’ื™ืช ื•ื ืื’ืจ ื‘ืจื–ืœ ื‘ืžืขืจื›ืช ื”ืขืฆื‘ื™ื ื”ืžืจื›ื–ื™ืช. ืžื—ืœื” ื–ื• ืฉื•ื ื”

ืžื”ืฆื•ืจื” ื”ื ื•ื™ืจื•ืœื•ื’ื™ืช ืฉืœ ืžื—ืœืช ื•ื™ืœืกื•ืŸ.ื›ืœื‘ื™ื ืžื’ื–ืข Bedlington terriers ืขืฉื•ื™ื™ื ืœืกื‘ื•ืœ ืžืžื—ืœืช ืื’ื™ืจืช ื ื—ื•ืฉืช ื”ื“ื•ืžื” ืžืื•ื“ ืœืžื—ืœืช ื•ื™ืœืกื•ืŸ. ืืฆืœ ื›ืœื‘ื™ื ืืœื• ื ืžืฆื ืฉื”ืคื’ื in vitro ื ืžืฆื ืฉืชื•ืฆืจ ื”ื’ืŸ MURR1. ื‘ื ื™ืกื™ื•ื ื•ืช ื ื’ืจื ืžืžื•ื˜ืฆื™ื” ื‘ื’ืŸ ื”ืžืฉืžืขื•ืช ืื‘ืœ ,WDP ืฉืœ ื”ืงืจื‘ื•ืงืกื™ืœื™ ืœืงืฆื” ื ืงืฉืจ MURR1ื”ืชืคืงื•ื“ื™ืช ืฉืœ ืžืžืฆื ื–ื” ืื™ื ื” ื™ื“ื•ืขื”. ื‘ืขื‘ื•ื“ืชื ืฉืœ ืฉื˜ืœืจ ื•ื—ื‘' ืžืฉื ืช 2004 ื ืžืฆื ืฉืฉื™ื ื•ื™ื™ื ืคื•ืœื™ืžื•ืจืคื™ื™ื ื‘ื’ืŸ ื–ื” ืขืฉื•ื™ื™ื ืœื”ืฉืคื™ืข ืขืœ ื”ื‘ื™ื˜ื•ื™

ื”ืคื ื•ื˜ื™ืคื™ ื‘ืงืจื‘ ื—ื•ืœื™ ื•ื™ืœืกื•ืŸ.

ืžื•ื˜ืฆื™ื•ืชืขื“ ื”ื™ื•ื ืชื•ืืจื• ื™ื•ืชืจ ืžโ€“500 ืžื•ื˜ืฆื™ื•ืช ื‘ื’ืŸ ATP7B. ื›โ€“60% ืžื”ืžื•ื˜ืฆื™ื•ืช ื”ืŸ ืžื•ื˜ืฆื™ื•ืช ืฉื‘ื”ืŸ ืžื•ื—ืœืคืช ื—ื•ืžืฆืช ืืžื™ื ื• ืื—ืช ื‘ืื—ืจืช, ื•ื”ืฉืืจ ื”ืŸ

ืžื—ืœืช ื•ื™ืœืกื•ืŸ: ืืกืคืงื˜ื™ื ื’ื ื˜ื™ื™ื ื‘ื™ืฉืจืืœ ืžืฉื” ืคืจื™ื“ืžืŸ

ื—ื™ื™ืงื” ืจื–ื ื™ืงึพื•ื•ืœืฃื”ืžื›ื•ืŸ ื”ื’ื ื˜ื™ ืข"ืฉ ื“ืื ืง ื’ืจื˜ื ืจ, ื‘ื™"ื— ืข"ืฉ ื—ื™ื™ื ืฉื™ื‘ื, ืจืžืช ื’ืŸ, ื•ื”ืคืงื•ืœื˜ื” ืœืจืคื•ืื” ืข"ืฉ ืกืืงืœืจ, ืื•ื ื™ื‘ืจืกื™ื˜ืช ืชืœ ืื‘ื™ื‘

ื”ื’ืŸ ATP7B ืžื•ื•ืกืช ืืช ื™ืฆื™ืจืช ื”ืฆืจื•ืœื•ืคืœื–ืžื™ืŸ, ื•ืœื›ืŸ ืืฆืœ ื—ื•ืœื™ ื•ื™ืœืกื•ืŸ

ืจืžื•ืช ื”ืื ื–ื™ื ื ืžื•ื›ื•ืช. ื ื•ืกืฃ ืœืชืคืงื™ื“ื• ื›ืžื•ื‘ื™ืœ ื ื—ื•ืฉืช, ืœืฆืจื•ืœื•ืคืœื–ืžื™ืŸ

ื™ืฉ ืชืคืงื™ื“ ืฉืœ ืคืจื•ืื•ืงืกื™ื“ื–, ื•ื‘ืงืจื‘

ื—ื•ืœื™ื ืฉืœื ื ืžืฆื ืืฆืœื ื›ืœืœ ืฆืจื•ืœื•ืคืœื–ืžื™ืŸ,

ืžืชืคืชื—ืช ืžื—ืœื” ื ื•ื™ืจื•ืœื•ื’ื™ืช ื•ื ืื’ืจ

ื‘ืจื–ืœ ื‘ืžืขืจื›ืช ื”ืขืฆื‘ื™ื ื”ืžืจื›ื–ื™ืช

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ืžืจืฅ 2012 ื”ืจืคื•ืื”update | ื—ืงืจ ื”ื›ื‘ื“

ืขื ื›ื ื™ืกืชื™ ืœืชืคืงื™ื“ ื™ื•"ืจ ื”ื—ื‘ืจื” ื—ืฉื‘ืชื™ ืฉืžืŸ ื”ืจืื•ื™ ืฉื™ื”ื™ื” ืœื—ื‘ืจื” ืฉืœื ื• ื›ืชื‘ ืขืช ืžืฉืœื”, ื•ืื›ืŸ ื›ืขื‘ื•ืจ ืฉื ื” ื™ื•ืฆื ืœืื•ืจ ื”ื’ื™ืœื™ื•ืŸ ื”ืจืืฉื•ืŸ ื•ื”ื—ื’ื™ื’ื™

ืฉืœ ื›ืชื‘ ื”ืขืช.ื‘ืจืฆื•ื ื™ ืœื”ื•ื“ื•ืช ืœืžืขืจื›ืช โ€œื”ืจืคื•ืื”": ืคืจื•ืค' ื™ื•ื–ืžื” ืขืœ ืฉืžืจ ืฉื•ืงื™ ื•ืคืจื•ืค' ืฉื™ื ืคืœื“ ื™ื”ื•ื“ื” ื‘ืจื•ื›ื” ื–ืืช ื•ืœืคืจื•ืค' ื™ืขืงื‘ ื‘ืจื•ืš ืฉืžื•ื ื” ืขืœโ€“ื™ื“ื™

ืœืขื•ืจืš ื”ืจืืฉื•ืŸ ืฉืœ ื”ืขื™ืชื•ืŸ.ื”ืขื™ืชื•ืŸ ื™ืฉืžืฉ ื‘ืžื” ืœืกืงื™ืจื•ืช ื•ืœื—ื™ื“ื•ืฉื™ื ื‘ื ื•ืฉืื™ื ืฉื•ื ื™ื ื‘ืชื—ื•ื ืžื—ืœื•ืช ื•ื”ืฉืชืœื•ืช ื”ื›ื‘ื“ ื•ื›ืŸ ืืคืฉืจ ื™ื”ื™ื” ืœื”ืชืขื“ื›ืŸ ื‘ื• ืขืœ ืื•ื“ื•ืช ื”ืคืขื™ืœื•ื™ื•ืช ื”ืฉื•ื ื•ืช ืฉืœ ื”ื—ื‘ืจื”. ื ื•ืกืฃ ืœื›ืš, ื‘ื›ืœ ื’ื™ืœื™ื•ืŸ ืชืคื•ืจืกื ืกืงื™ืจื” ืฉืœ ื”ื ื•ืฉืื™ื ืฉื”ื•ืฆื’ื• ื‘ื›ื ืก ื”ื—ื“โ€“ื™ื•ืžื™ ื”ืฉื ืชื™ ืฉืœ ื”ื—ื‘ืจื” ื•ื”ืชืงืฆื™ืจื™ื ืฉื”ื•ืฆื’ื• ื‘ื›ื ืก ืกื•ืฃ ื”ืฉื‘ื•ืข ืฉืœ ื”ื—ื‘ืจื”. ื‘ื’ื™ืœื™ื•ืŸ ื–ื” ืžืชืคืจืกืžืช ืกืงื™ืจื” ืขืœ ื”ืงืฉืจ ื‘ื™ืŸ ื”ื›ื‘ื“ ืœื›ืœื™ื”, ื ื•ืฉื ืฉื”ื•ืฆื’ ื‘ื›ื ืก ื”ื—ื“โ€“ื™ื•ืžื™ ืฉืœ ื”ื—ื‘ืจื” ื‘ืกืคื˜ืžื‘ืจ 2011,

ื•ื”ืชืงืฆื™ืจื™ื ืฉื ื‘ื—ืจื• ืœื”ืฆื’ื” ื‘ื›ื ืก ื”ื—ื‘ืจื” ื‘ื›ืคืจ ื‘ืœื•ื 2012.ื”ืขื™ืชื•ืŸ ืžืฉืžืฉ ืœื”ืขื‘ืจืช ืžื™ื“ืข ื—ื“ืฉื ื™ ื•ืขื“ื›ื ื™ ื‘ื›ืœ ื”ืงื˜ื’ื•ืจื™ื•ืช ืฉื‘ื”ืŸ ืื ื• ืขื•ืกืงื™ื ืœืฆื•ืจืš ื”ืขืžืงืช ื”ื™ื“ืข ื”ืŸ ื‘ื ื•ืฉืื™ื ื”ื‘ื•ืขืจื™ื ื”ืงืฉื•ืจื™ื ื‘ืขื‘ื•ื“ื” ื”ืฉื•ื˜ืคืช ื”ื™ื•ืžื™ื•ืžื™ืช ื•ื”ืŸ ื‘ืจืขื™ื•ื ื•ืช ื—ื“ืฉื ื™ื™ื ืœื‘ื™ืฆื•ืข ืžื—ืงืจื™ื ืคื•ืจื” ื›ืจ ืœื”ื•ื•ืช ื™ื›ื•ืœ ื–ื” ืžื™ื“ืข ื‘ืกื™ืกื™ื™ื ื‘ืžืขื‘ื“ื•ืช ื”ืžื—ืงืจ ืฉืœื ื•. ืœืฉื™ืชื•ืคื™ ืคืขื•ืœื” ื‘ืจืžื” ื”ืืจืฆื™ืช ื‘ื™ืŸ ื”ืžืจื›ื–ื™ื ื”ืฉื•ื ื™ื ืœืฆื•ืจืš ืžื—ืงืจื™ื ืงืœื™ื ื™ื™ื ืžืฉื•ืชืคื™ื ืžืฆื“ ืื—ื“, ื•ืœืฆื•ืจืš ื”ื‘ืืช ืžื—ืงืจื™ื ืงืœื™ื ื™ื™ื ืžื—ื‘ืจื•ืช ื”ืคืืจืžื” ืœืืจืฅ ืžืฆื“ ืฉื ื™. ื ื•ืกืฃ ืœื›ืš ื”ืชื‘ืจื›ื ื• ื‘ื—ื•ืงืจื™ื ืžืขื•ืœื™ื ื‘ืฉื˜ื— ืžื—ืœื•ืช ื•ื”ืฉืชืœื•ืช ื”ื›ื‘ื“, ื•ื”ืœืœื• ืชื•ืจืžื™ื ืœืงื™ื“ื•ื ื”ื”ืคื˜ื•ืœื•ื’ื™ื” ื‘ืจืžื” ื”ืœืื•ืžื™ืช ื•ื”ื‘ื™ืŸโ€“ืœืื•ืžื™ืช, ื•ื”ื ืกืžื›ื•ืช ืžืงืฆื•ืขื™ืช ื‘ืืจื”"ื‘ ื•ื‘ืื™ืจื•ืคื”. ื—ื•ืงืจื™ื ืืœื” ื™ื›ื•ืœื™ื ืœื”ืจื™ื ืืช ื”ื›ืคืคื” ื•ืœืคืชื— ื™ื•ื–ืžื•ืช ืฉืœ ืžื—ืงืจื™ื ืงืœื™ื ื™ื™ื ื•ืžื—ืงืจื™ ื‘ืกื™ืก ืžืฉื•ืชืคื™ื ืœืžืจื›ื–ื™ื ืฉื•ื ื™ื, ื•ื”ืขื™ืชื•ืŸ ื™ื›ื•ืœ ืœืฉืžืฉ

ืžื ื•ืฃ ืœืงื™ื“ื•ื ื™ื•ื–ืžื•ืช ืืœื”.ื‘ื’ื™ืœื™ื•ืŸ ื–ื” ื‘ื—ืจ ื”ืขื•ืจืš ืœื”ืชืขืžืง ื‘ื ื•ืฉืื™ื ืืœื•: ื—ื™ื“ื•ืฉื™ื ื‘ื˜ื™ืคื•ืœ ื‘ื”ืคื˜ื•ืฆืœื•ืœืจ ืงืจืฆื™ื ื•ืžื”, ืชืจื•ืคื•ืช ื”ืžืขืœื•ืช ืืช ื”ืจื’ื™ืฉื•ืช ืœืื™ื ืกื•ืœื™ืŸ ืœื˜ื™ืคื•ืœ ื‘ื›ื‘ื“ ื”ืฉื•ืžื ื™, ื—ื™ื“ื•ืฉื™ื ื‘ืชื—ื•ื ื”ื—ื™ืกื•ืŸ ืœื”ืคื˜ื™ื˜ื™ืก B ื•ื—ืฉื™ื‘ื•ืช

ื”ื’ื ื˜ื™ืงื” ื‘ืžื—ืœืช ื•ื™ืœืกื•ืŸ.ื”ืฉื ื” ื ื›ื ืกื• ืœืกืœ ื”ื‘ืจื™ืื•ืช ื”ืชืจื•ืคื•ืช ื”ื—ื“ืฉื•ืช ืžืงื‘ื•ืฆืช ืžืขื›ื‘ื™ ื”ืคืจื•ื˜ื™ืื–ื•ืช. ืชืจื•ืคื•ืช ืืœื• ื”ืŸ ืคืจื™ืฆืช ื“ืจืš ืžืฉืžืขื•ืชื™ืช ื‘ื˜ื™ืคื•ืœ ื‘ื–ื™ื”ื•ื ื›ืจื•ื ื™ ื‘ื ื’ื™ืฃ ื”ื”ืคื˜ื™ื˜ื™ืก C. ืขืœ ื›ืŸ ืขื•ืžื“ ื‘ืคื ื™ ื”ื—ื‘ืจื” ืืชื’ืจ ื—ืฉื•ื‘ ื‘ื™ื•ืชืจ ื•ื”ื•ื ื”ืชื•ื•ื™ื™ืช ืงื•ื•ื™ื ืžื ื—ื™ื ื‘ืจื•ืจื™ื ื•ืื—ื™ื“ื™ื ืœื˜ื™ืคื•ืœ ื”ืกื˜ื ื“ืจื˜ื™ ื”ื—ื“ืฉ ื‘ื–ื™ื”ื•ื ื›ืจื•ื ื™ ื‘ื ื’ื™ืฃ ื”ื”ืคื˜ื™ื˜ื™ืก C. ื‘ื’ื™ืœื™ื•ืŸ ื–ื” ืžืชืคืจืกื ืžืืžืจ ืžืขืจื›ืช

ื—ืฉื•ื‘ ื‘ื ื•ืฉื ื–ื” ืœืฆื•ืจืš ื”ืขืžืงืช ื”ื™ื“ืข ื•ื”ืžื•ื“ืขื•ืช ื‘ืชื—ื•ื ื—ืฉื•ื‘ ื–ื”. ื‘ืชืงื•ืคื” ื–ืืช ืžืชืžื ื™ื ืžื ื”ืœื™ื ื—ื“ืฉื™ื ื‘ื™ื—ื™ื“ื•ืช/ืžื›ื•ื ื™ ื”ื›ื‘ื“ ื‘ืืจืฅ. ืื ื™ ืจื•ืฆื” ืœืื—ืœ ืœื›ื•ืœื ื”ืฆืœื—ื” ื‘ืชืคืงื™ื“ ื”ื—ื“ืฉ. ืื ื™ ื‘ื˜ื•ื—ื” ืฉืžื ื”ืœื™ื ืืœื” ื™ื•ื‘ื™ืœื• ืชื—ื•ื ื–ื” ืฉืœ ืžื—ืœื•ืช ื•ื”ืฉืชืœื•ืช ื›ื‘ื“ ื‘ืื•ืคืŸ ื”ืžืงืฆื•ืขื™ ื‘ื™ื•ืชืจ ื•ื‘ืœื™ื•ื•ื™ ืžื—ืงืจื™ื ืงืœื™ื ื™ื™ื ื•ื‘ืกื™ืกื™ื™ื ืžืฉืžืขื•ืชื™ื™ื, ื›ืš ืฉืฉื˜ื— ื”ื”ืคื˜ื•ืœื•ื’ื™ื”

ื‘ืืจืฅ ื™ื”ื™ื” ืžื•ืงื“ ืžืฉื™ื›ื” ื•ื™ืงืจื•ืฅ ืœืจื•ืคืื™ื ืฆืขื™ืจื™ื ืจื‘ื™ื.ืœืกื™ื•ื, ื”ืฆืœื—ืช ื”ืขื™ืชื•ืŸ ื˜ืžื•ื ื” ื‘ืชืจื•ืžื” ืฉืœ ื›ืœ ืื—ื“ ื•ืื—ืช ืžืืชื ื•. ืื ื™ ืžื–ืžื™ื ื” ืืชื›ื ืœืงื—ืช ื—ืœืง ื‘ืžื™ื–ื ื—ืฉื•ื‘ ื–ื”. ืื ื ื›ืชื‘ื• ืชื’ื•ื‘ื•ืช,

ื”ืขื™ืจื•/ื”ืื™ืจื• ืขืœ ื”ื ืืžืจ ื•ืชืจืžื• ืœื”ืฆืœื—ืชื•.

ื‘ื‘ืจื›ืช ื›ื ืก ืžื•ืฆืœื— ื•ื”ืžืฉืš ื›ืชื™ื‘ื” ืคื•ืจื™ื™ื”,ืคืจื•ืคืกื•ืจ ื–ื™ื• ื‘ืŸ ืืจื™ื™ื•"ืจ ื”ื—ื‘ืจื” ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“ื•ืขื•ืจื›ืช ืžืฉื ื”

ื“ื‘ืจ ื”ื™ื•"ืจ

ื“ื‘ืจ ื”ืขื•ืจืšืœื“ืจืš. ื™ื•ืฆื ื”ื›ื‘ื“ ืื•ื”ื‘ื™ ืฉืœ ื”ืจืืฉื•ืŸ ื”ื’ื™ืœื™ื•ืŸ

ืชื•ื“ืชื ื• ืœืžื—ื‘ืจื™ ื”ืžืืžืจื™ื ื”ืจืืฉื•ื ื™ื.ืœืงืจืืช ืคืจืกื•ื ื”ื”ื ื—ื™ื•ืช ื”ืงืœื™ื ื™ื•ืช ื”ืื™ืจื•ืคืื™ื•ืช ืœื’ื‘ื™ ื˜ื™ืคื•ืœ ื‘ืžื—ืœืช ื•ื™ืœืกื•ืŸ, ื”ื–ืžื ื• ืืช ืคืจื•ืคืกื•ืจ ืžืฉื” ืคืจื™ื“ืžืŸ, ืžื’ืœื” ืžื™ืงื•ื ื”ื’ืŸ ืœืžื—ืœื”, ืœื”ืื™ืจ ืืช ืขื™ื ื™ื ื• ื‘ืืฉืจ ืœืชืคืงื™ื“ ื”ื’ื ื˜ื™ืงื” ื‘ืžื—ืœื” ื–ืืช

ื•ื—ืœืงื” ื‘ื™ืฉืจืืœ.ื”ื›ื ืก ื”ืžื•ืฆืœื— โ€œื”ื›ื‘ื“ ืคื•ื’ืฉ ืืช ื”ื›ืœื™ื”" ืžืกื•ื›ื ื›ืืŸ ื‘ืžื“ื•ื™ืง ืขืœโ€“ื™ื“ื™ ื“"ืจ ื™ืขืงื‘ ืžืื•ืจ. ืขื•ื“ ืžื•ื‘ืื™ื ืžืืžืจื™ื ื‘ื ื•ืฉืื™ื ื”ื‘ื•ืขืจื™ื ื”ืžืขืกื™ืงื™ื ืื•ืชื ื• ื•ืืช ื”ืกืคืจื•ืช ื‘ืชื—ื•ื ื”ื›ื‘ื“ - ืคืจื™ืฆืช ื”ื“ืจืš ื‘ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช, ื”ื’ื™ืฉื” ื”ืืงื˜ื™ื‘ื™ืช ืžืฆื™ืœืช ื—ื™ื™ื ืœโ€“HCC ื•ืžื ื™ืขืช HBV. ื ื•ืกืฃ ืœื›ืš ืžื•ื‘ืืช

.NASH ืชื’ื•ื‘ื” ืœืžืืžืจ ื—ืฉื•ื‘ ื‘ืกืคืจื•ืช ื”ืจืคื•ืื™ืช ื‘ื ื•ืฉื ืฉืœ

ืœื ื•ื—ื•ืชื›ื ืฆื™ืจืคื ื• ืืช ืชืงืฆื™ืจื™ ื”ื›ื ืก ืฉืœ ื”ื—ื‘ืจื” ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“ ืฉื™ื™ืขืจืš ื‘ื›ืคืจ ื‘ืœื•ื.

ื›ืชื‘ ื”ืขืช, ื›ืคื™ ืฉื”ื’ื“ื™ืจ ื–ืืช ืคืจื•ืคืกื•ืจ ืฉื™ื ืคืœื“ ืขื•ืจืš "ื”ืจืคื•ืื”", ื”ื•ื โ€œืฉืœื ื•". ืืชื ืžื•ื–ืžื ื™ื ืœื›ืชื•ื‘ ืชื’ื•ื‘ื•ืช ืžื•ืฉื›ืœื•ืช ืœืžืืžืจื™ื ื—ืฉื•ื‘ื™ื

ื‘ืขื™ืชื•ื ื•ืช ื”ื›ืœืœื™ืช ืื• ืœืขื“ื›ืŸ ื‘ื ื•ืฉืื™ื ื—ืฉื•ื‘ื™ื.

ื‘ื‘ืจื›ืช ื›ื ืก ืžื•ืฆืœื—ื•ื”ืžืฉืš ื›ืชื™ื‘ื” ืคื•ืจื™ื™ื”,ืคืจื•ืคืกื•ืจ ื™ืขืงื‘ ื‘ืจื•ืšืขื•ืจืš ื›ืชื‘ ื”ืขืช

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ื’ื™ืœื™ื•ืŸ ืžืก' 1 | ืžืจืฅ 2012ื›ืชื‘ ื”ืขืช ืฉืœ ื”ื—ื‘ืจื” ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“

shutterstock.com :ืฆื™ืœื•ื ื”ืฉืขืจ

ืžื‘ื™ืช ื”ื”ืกืชื“ืจื•ืช ื”ืจืคื•ืื™ืช ื‘ื™ืฉืจืืœ

ื—ื‘ืจื™ ืžืขืจื›ืช

ืขื•ืจืš: ืคืจื•ืค' ื™ืขืงื‘ ื‘ืจื•ืš

ืขื•ืจื›ืช ืžืฉื ื”: ืคืจื•ืค' ื–ื™ื• ื‘ืŸ ืืจื™

ืขื•ืจื›ื™ื ื™ื•ืขืฆื™ื: ืคืจื•ืค' ื™ื”ื•ื“ื” ืฉื™ื ืคืœื“

ืคืจื•ืค' ื™ื”ื•ืฉืข )ืฉื•ืงื™( ืฉืžืจืคืจื•ืค' ื’ื“ ืงืจืŸ

ื›ืชื•ื‘ืช ื”ืžืขืจื›ืช: ืจื—' ื–'ื‘ื•ื˜ื™ื ืกืงื™ 35, ื‘ื ื™ื™ืŸ ื”ืชืื•ืžื™ื 2,

ืช"ื“ 3566, ืจืžืช ื’ืŸ, ืžื™ืงื•ื“ 52136ื˜ืœ': 03-6100430, ืคืงืก: 03-7519673

[email protected] :ื“ื•ื"ืœ

ื›ืœ ื”ืžื•ื“ืขื•ืช ื”ืžืชืคืจืกืžื•ืช ื‘ืขื™ืชื•ืŸ ื”ืŸ ืขืœ ืื—ืจื™ื•ืช ื”ืžืคืจืกืžื™ื ื‘ืœื‘ื“. ื›ืžื•ึพื›ืŸ ื’ื ืชื•ื›ืŸ ื”ืžืืžืจื™ื ื”ื•ื ืขืœ ืื—ืจื™ื•ืช ื”ื›ื•ืชื‘ื™ื ื‘ืœื‘ื“.

ืœืขื•ืจื›ื™ ื”ืขื™ืชื•ืŸ ื•ืœื”ืกืชื“ืจื•ืช ื”ืจืคื•ืื™ืช ื‘ื™ืฉืจืืœ ืื™ืŸ ื›ืœ ืื—ืจื™ื•ืช ืœืชื•ื›ืŸ ื”ืžื•ื“ืขื•ืช

ื•ื”ืžืืžืจื™ื.

ืคืจืกื•ื ื•ืฉื™ื•ื•ืง: ืงื‘ื•ืฆืช ืžื“ื™ื” ืคืืจื ืืžื™ืจ ื“ื•ืจื•ืŸ: 050-5569003

ื’ื•ืœืŸ ืคืจืฅ: 050-3003304www.mediafarm.co.il

ื“ื‘ืจื™ ืคืชื™ื—ื” 03ื“ื‘ืจ ื”ืขื•ืจืš: ืคืจื•ืค' ื™ืขืงื‘ ื‘ืจื•ืš

ื“ื‘ืจ ื”ื™ื•"ืจ: ืคืจื•ืค' ื–ื™ื• ื‘ืŸ ืืจื™

ืžื—ืœืช ื•ื™ืœืกื•ืŸ: ืืกืคืงื˜ื™ื 05 ื’ื ื˜ื™ื™ื ื‘ื™ืฉืจืืœ

ืžืฉื” ืคืจื™ื“ืžืŸ ื•ื—ื™ื™ืงื” ืจื–ื ื™ืงึพื•ื•ืœืฃ

ื”ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ 08 ื ื’ื™ืคื™ืช 2012: ืคืจื™ืฆืช ื“ืจืš

ืืœื™ ืฆื•ืงืจืžืŸ

ืกืจื˜ืŸ ื›ื‘ื“ ืจืืฉื•ื ื™ 12ืจื™ืคืขืช ืกืคื“ื™

ืขื“ื›ื•ื ื™ื ื‘ืžื—ืœื•ืช ื›ื‘ื“: ืจืฉืžื™ื 15ืžื”ื›ื ืก ื”ื—ื“ึพื™ื•ืžื™ ืฉืœ ื”ื—ื‘ืจื”

ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“ ื‘ืฉื™ืชื•ืฃ ืขื ื”ืื™ื’ื•ื“ ื”ื™ืฉืจืืœื™ ืœื ืคืจื•ืœื•ื’ื™ื” -

โ€œื”ื›ื‘ื“ ืคื•ื’ืฉ ืืช ื”ื›ืœื™ื”" - 6 ื‘ืกืคื˜ืžื‘ืจ 2011

ื™ืขืงื‘ ืžืื•ืจ

ื˜ื™ืคื•ืœ ื‘ื›ื‘ื“ ืฉื•ืžื ื™ ืฉืœื ืขืœ ืจืงืข 19ืืœื›ื•ื”ื•ืœ ื‘ืืžืฆืขื•ืช ืชืจื•ืคื•ืช ืžืกื•ื’

INSULIN SENSITIZERืชื’ื•ื‘ื” ืœืžืืžืจ:

Insulin sensitisers in the treatment of non-alcoholic fattyliver disease: a systematic review

ื—ื ื™ ื™ืฉื•ืขื”, ืฉื™ืจื” ื–ืœื‘ืจึพืฉื’ื™ื ื•ืจืŸ ืื•ืจืŸ

ื—ื™ืกื•ื ื™ื ืœื ื’ื™ืฃ ื“ืœืงืช 18 ื”ื›ื‘ื“ ืžืกื•ื’ B - ืขื“ื›ื•ืŸ

ืื•ืจืŸ ืฉื‘ื•ืœืช ื•ืื“ื ืคื™ืœื™ืคืก

ืชืงืฆื™ืจื™ ื”ืžืืžืจื™ื ืฉื™ื•ืฆื’ื• 22 ื‘ืžื”ืœืš ื”ื›ื ืก ื”ืฉื ืชื™ ืฉืœ ื”ื—ื‘ืจื”

ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“

ื•ืขื“ ื”ื—ื‘ืจื” ืœื—ืงืจ ื”ื›ื‘ื“ ืžื‘ืจืš ืืช ื”ืจื•ืคืื™ื ื”ื—ื‘ืจื™ื ื”ืžืฉืชืชืคื™ื ื‘ื›ื ืก ื”ืฉื ืชื™

ืฉืœ ื”ื—ื‘ืจื” ืœื—ืงืจ ื”ื›ื‘ื“ ื•ืžืื—ืœ ืœื›ื•ืœื ื• ื›ื ืก ืžื”ื ื” ื•ืคื•ืจื”

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ืžืจืฅ 2012

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ื—ืงืจ ื”ื›ื‘ื“ | updateื”ืจืคื•ืื”ื‘ื“

ื”ื›ื˜ืŸ

ืกืจ

ื ื• ืžืคืจืกืžื™ื ืขื“ื›ื•ืŸ ื–ื” ืœืื•ืจ ืคืจืกื•ืžื• ืฉืœ ืžืืžืจ ื”ืกืงื™ืจื” ืืฉืœ ืกื™ืจืื–ืณ ื•ื—ื‘ืจื™ื• ื‘ื ื•ืฉื ืกืจื˜ืŸ ื›ื‘ื“ )ืก"ื›(, ืฉื”ื•ื ื”ื—ืžื™ืฉื™ ื‘ืฉื›ื™ื—ื•ืชื• ื‘ืงืจื‘ ื’ื‘ืจื™ื ื•ืฉื‘ื™ืขื™ ื‘ืฉื›ื™ื—ื•ืชื• ื‘ืงืจื‘ ื ืฉื™ื ื‘ืขื•ืœื ]2,1[. ื›ืขืฉืจื™ื ืืœืฃ ืžืงืจื™ื ื—ื“ืฉื™ื ืžืชื’ืœื™ื ืžื“ื™ ืฉื ื” ื‘ืืจืฆื•ืช ื”ื‘ืจื™ืช. ืžืจื‘ื™ืช ื”ืชื—ืœื•ืื”, ื›โ€“85%, ืงื•ืจื™ืช ื‘ืžื“ื™ื ื•ืช ืžืชืคืชื—ื•ืช, ืฉื‘ื”ืŸ ืกื•ื‘ืœื™ื ืžื–ื™ื”ื•ื ืื ื“ืžื™ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืžืกื•ื’ Bื )HBV(. ืก"ื› ืžื•ืคื™ืข ืœืขืชื™ื ื ื“ื™ืจื•ืช ืœืคื ื™ ื’ื™ืœ 40, ื•ืฉื™ื ื”ื•ืคืขืชื• ื‘ื’ื™ืœ 70. ืฉื›ื™ื—ื•ืช ืก"ื› ื‘ืงืจื‘ ื’ื‘ืจื™ื ื’ื‘ื•ื”ื” ืคื™ 4-2 ืžืฉื›ื™ื—ื•ืชื• ื‘ืงืจื‘ ื ืฉื™ื. ืก"ื› ื”ืžื™ื•ื—ืก ืœื–ื™ื”ื•ื ื‘ื ื’ื™ืฃ ื”ื›ื‘ื“ ืžืกื•ื’ Cื )HCV( ื”ื•ืคืš ืœื”ื™ื•ืช ืกื™ื‘ืช ื”ืžื•ื•ืช ืชืœื•ื™ื™ืชโ€“ืกืจื˜ืŸ ื”ืžื•ื‘ื™ืœื” ื‘ืืจืฆื•ืช ื”ื‘ืจื™ืช. ื”ื™ืืจืขื•ืช ืก"ื› ื‘ืืจืฆื•ืช ื”ื‘ืจื™ืช ืขืœืชื” ื‘ืฉื ื™ ื”ืขืฉื•ืจื™ื ื”ืื—ืจื•ื ื™ื, ืืš ื”ืžืžื•ืฆืข ืฉืœ ื”ื™ืฉืจื“ื•ืช ืœโ€“5 ืฉื ื™ื ื ื•ืชืจ ื ืžื•ืš

ืžโ€“12%.ื ื’ื™ืคื™ืช ืžืกื•ื’ ื’ื•ืจืžื™ ื”ืกื™ื›ื•ืŸ ื”ืขื™ืงืจื™ื™ื ืœืก"ื› ื›ื•ืœืœื™ื ื“ืœืงืช ื›ื‘ื“ C, ืžื—ืœืช ื›ื‘ื“ ืืœื›ื•ื”ื•ืœื™ืช ื•ื›ื›ืœ ื”ื ืจืื” ืžื—ืœืช ื›ื‘ื“ ืฉื•ืžื ื™ ืœื B ืื• ืืœื›ื•ื”ื•ืœื™ืช ]2[. ื’ื•ืจืžื™ ืกื™ื›ื•ืŸ ืฉื›ื™ื—ื™ื ืคื—ื•ืช ื”ื ื”ืžื•ื›ืจื•ืžื˜ื•ื–ื™ืก ืžื•ืœื“ืช, ื—ืกืจ ื‘โ€“ฮฑ1 ืื ื˜ื™โ€“ื˜ืจื™ืคืกื™ืŸ, ื“ืœืงืช ื›ื‘ื“ ืื•ื˜ื•ืื™ืžื•ื ื™ืช, ื—ืœืง ืžื”ืคื•ืจืคื™ืจื™ื•ืช

ื•ืžื—ืœืช ื•ื™ืœืกื•ืŸ. ื™ืฉ ืฉื•ื ื™ ืจื‘ ื‘ืคื™ื–ื•ืจ ืฉืœ ื’ื•ืจืžื™ ืกื™ื›ื•ืŸ ืืœื• ื‘ืงืจื‘ ื—ื•ืœื™ ืก"ื›, ื•ื”ื•ื ืชืœื•ื™ ื‘ืื–ื•ืจ ื’ื™ืื•ื’ืจืคื™ ืืฆืœ ื ืžืฆืื” ืฉื—ืžืช ื•ื‘ืžื•ืฆื. ืกืจื˜ืŸ ืžื—ื•ืœื™ 90% ืขื“ 80%ื”ื›ื‘ื“. ื‘ืขื•ืœื, ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืœืžื—ืฆื™ืช ื”ื’ื•ืจื ื”ื™ื B ืžืกื•ื’

ืžืงืจื™ ืก"ื› ื‘ืื•ืคืŸ ื›ืœืœื™ ื•ืœื›ืœ ื”ืžืงืจื™ื ื‘ืงืจื‘ ื™ืœื“ื•ืช. ืืžื ื ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืžืกื•ื’ B ื™ื›ื•ืœื” ืœื’ืจื•ื ืœืก"ื› ืœืœื ืฉื—ืžืช, ืืš ืœืจื•ื‘ )70%-80%( HBV ืœื—ืœื•ืช ื‘ืก"ื› ืขื•ืœื” ื™ืฉ ืฉื—ืžืช ื‘ืžืงืจื™ื ืืœื•. ื”ืกื™ื›ื•ืŸ ืฉืœ ื ืฉืื™ ื‘ืžื™ื•ื—ื“ ื‘ืงืจื‘ ื’ื‘ืจื™ื ืื• ืžื‘ื•ื’ืจื™ื ื”ืกื•ื‘ืœื™ื ืžื–ื™ื”ื•ื ืžืžื•ืฉืš, ื•ืืฉืจ ื ื—ืฉืคื• ืœืืคืœืื˜ื•ืงืกื™ืŸ, ืฆืจื›ื• ืืœื›ื•ื”ื•ืœ ืื• ืขื™ืฉื ื•, ื ื“ื‘ืงื• ื‘ื–ื™ื”ื•ื ื ื•ืกืฃ - HCV ืื• HDV ืื• ืฉื”ืขื•ืžืก ื”ื ื’ื™ืคื™ ืฉืœื”ื ื’ื‘ื•ื”, ื•ื›ืŸ ื ื“ื‘ืงื™ื ืขื ื’ื ื•ื˜ื™ืค C. ื’ื•ืจืžื™ ืกื™ื›ื•ืŸ ืœืกืจื˜ืŸ ื›ื‘ื“ ื‘ืงืจื‘ ื—ื•ืœื™ HCV ื›ื•ืœืœื™ื ื’ื™ืœ ืžื‘ื•ื’ืจ ื‘ืขืช ,HBVโ€“ืื• ื‘ immunodeficiency virusโ€“ื”ื”ื™ื“ื‘ืงื•ืช, ื’ื‘ืจื™ื, ื–ื™ื”ื•ื ื ื•ืกืฃ ื‘ื•ื›ื›ืœ ื”ื ืจืื” ืกื•ื›ืจืช ืื• ื”ืฉืžื ื”. ืฆืจื™ื›ื” ืžืจื•ื‘ื” ื•ืžืžื•ืฉื›ืช ืฉืœ ืืœื›ื•ื”ื•ืœ ื”ื•ื›ื—ื” ื›ื’ื•ืจื ืžื’ื‘ื™ืจ ืกื™ื›ื•ืŸ ืœื”ื•ืคืขืช ืกืจื˜ืŸ ื”ื›ื‘ื“ ื”ืŸ ื‘ืื•ืคืŸ ื‘ืœืชื™ ืชืœื•ื™ .HBVโ€“ื•ื‘ืงืฉืจ ื—ืœืฉ ื™ื•ืชืจ ื’ื ืชืœื•ื™ื” ื‘ื–ื™ื”ื•ื ื‘ ,HCVโ€“ื•ื”ืŸ ื›ืชืœื•ืช ื‘ื–ื™ื”ื•ื ื‘ื–ื™ื”ื•ื ืื ื˜ื™โ€“ื•ื™ืจืืœื™ ืžืจืกืŸ ื•ื˜ื™ืคื•ืœ HBV ื ื’ื“ ื—ื™ืกื•ืŸ ื›ืžื• ื˜ื™ืคื•ืœื™ื ืœืก"ื›, ื”ืกื™ื›ื•ืŸ ืืช ืžื•ืจื™ื“ื™ื ืคืขื™ืœื™ื, ืœื—ื•ืœื™ื HCV ืžืกืœืง ืื• HBVืืš ืœื ืžืขืœื™ืžื™ื ืื•ืชื• ื—ืœื•ื˜ื™ืŸ. ืขืœ ืคื™ ื”ื ื—ื™ื•ืช ื”ื˜ื™ืคื•ืœ ืฉืœ ื”ืืจื’ื•ืŸ ื”ืืžืจื™ืงืื™ ืœื—ืงืจ ื”ื›ื‘ื“, ืžื•ืžืœืฅ ืœื‘ืฆืข ืœื—ื•ืœื™ื ื‘ืกื™ื›ื•ืŸ ืžื•ื’ื‘ืจ ืกืจื™ืงื” ืœืื™ืชื•ืจ ืก"ื›. ื”ื”ืžืœืฆื” ื”ืžืงื•ื‘ืœืช ื”ื™ื•ื ื”ื™ื ืœื‘ืฆืข ืกืจื™ืงื” ื‘ืขื–ืจืช AFP ืคืขื ื‘ืฉื™ืฉื” ื—ื•ื“ืฉื™ื ืœื›ืœ ื”ื—ื•ืœื™ื ื”ืกื•ื‘ืœื™ื ืกื•ื ืจ ื‘ื˜ืŸ ื•ืจืžืช ืžืฉื—ืžืช ื›ื‘ื“ ืื• ืžืคื™ื‘ืจื•ื–ื™ืก ืžืชืงื“ื, ืœืœื ืงืฉืจ ืœืžื—ืœืช ืจืงืข. ื ื™ืกื™ื•ืŸ ืฉื ืขืฉื” ื‘ืฆืคื•ืŸ ืืžืจื™ืงื” ืœื”ืขืจื™ืš ืกืžืžื ื™ื ื‘ื™ื•ืœื•ื’ื™ื™ื ืื—ืจื™ื ื ื›ืฉืœ,

ืœืจื‘ื•ืช des-gamma-carboxyprothrombin ืื• AFP ื”ืงืฉื•ืจ ืœืœืฆื™ื˜ื™ืŸ. ื˜ื•ืžื•ื’ืจืคื™ื” ืžืžื•ื—ืฉื‘ืช )CT( ื•ืชื”ื•ื“ื” ืžื’ื ื˜ื™ืช )MRI( ืื™ื ืŸ ืžื•ืžืœืฆื•ืช ื•ื”ื™ื™ื—ื•ื“ื™ื•ืช ื‘ืกืงื™ืจืช ืก"ื› ืžื•ืงื“ืžืช, ืฉื›ืŸ ืขื“ื™ื™ืŸ ืœื ื ืœืžื“ื” ื”ืจื’ื™ืฉื•ืช

ื‘ื‘ื“ื™ืงื•ืช ืืœื• ื•ื”ืŸ ื›ืจื•ื›ื•ืช ื‘ืขืœื•ื™ื•ืช ื’ื‘ื•ื”ื•ืช ื•ื‘ื—ืฉื™ืคื” ืœืงืจื™ื ื”.ื’ื•ื“ืœ ื”ื’ื™ื“ื•ืœ. ื‘ืžืงืจื™ื ืฉืœ ืฉื—ืžืช ื”ื’ื™ืฉื” ื”ืงืœื™ื ื™ืช ืžื‘ื•ืกืกืช ืขืœ ื•ื”ื•ืคืขืช ื’ื•ืฉ ื‘ื›ื‘ื“ ืฉืงื•ื˜ืจื• ื’ื“ื•ืœ ืžืฉื ื™ ืก"ืž, ื”ืื‘ื—ื ื” ื™ื›ื•ืœื” ืœื”ืชื‘ืกืก ืขืœ ืžืืคื™ื™ื ื™ ื”ื“ืžื™ื” ื˜ื™ืคื•ืกื™ื™ื ืฉืœ ื”ืื“ืจื” ืขื•ืจืงื™ืช ืžื•ืงื“ืžืช ื•ืฉื˜ื™ืคื” ืžื”ื™ืจื” ื‘ืฉืœื‘ ื•ืจื™ื“ื™ ืื• ืžืื•ื—ืจ ืฉืœ CT ืจื‘โ€“ืฉืœื‘ื™ )ื‘ืœื™ ื—ื•ืžืจ ื ื™ื’ื•ื“ ื‘ืฉืœื‘ ืขื•ืจืงื™, ืฉืœื‘ ื•ืจื™ื“ื™ ื•ืฉืœื‘ ืžืื•ื—ืจ(, ืื• ืฉืœ MRI ื“ื™ื ืžื™ ืขื ื’ื“ื•ืœื™ื ื™ื•ื. ืฉื™ื ื•ื™ื™ ื”ื“ื™ืžื•ืช ื”ืžืฆื‘ื™ืขื™ื ืขืœ ื”ืื“ืจื” ืžื•ืงื“ืžืช ืžืชื‘ืกืกื™ื ืขืœ ื”ืขืฉืจืช ื”ื’ื•ืฉ ื‘ื›ืœื™ ื“ื ืฉืžืงื•ืจื ื‘ืขื•ืจืง ื”ื›ื‘ื“. ื›ืืฉืจ ืงื•ื˜ืจ ื”ื ื’ืข ื‘ื›ื‘ื“ ืฉืœ ื—ื•ืœื” ืฉื—ืžืช ื ืข ื‘ื™ืŸ 1 ืœโ€“2 ืก"ืž, ืžื•ืžืœืฅ ืœืงื‘ืœ ืชื™ืžื•ืš ื‘ืจื ื˜ื’ืŸ ื‘ืืžืฆืขื•ืช ืฉืชื™ ืฉื™ื˜ื•ืช ื“ื™ืžื•ืช ื“ื™ื ืืžื™ื•ืช ื™ื—ื“ื™ื•. ื™ืฉ ืœืฉืงื•ืœ ื‘ื™ื•ืคืกื™ื” ืžื”ืžืžืฆื ื‘ื›ื‘ื“ ื‘ื”ื“ืจื›ืช ืจื ื˜ื’ืŸ ื›ืฉื ืจืื™ืช ื”ืชื ื”ื’ื•ืช ืœื ื˜ื™ืคื•ืกื™ืช ืฉืœื•, ื›ืฉื™ืฉ ืกืชื™ืจื” ื‘ื™ืŸ ื”ื”ื“ืžื™ื•ืช

ื”ื“ื™ื ืืžื™ื•ืช, ืื• ื›ืฉื™ืฉ ื—ืฉื“ ืœืžืžืื™ืจื•ืช ืฉืœ ื”ื ื’ืขื™ื ืœืœื ืฉื—ืžืช.ื”ืกื›ื ื” ืฉืœ ืคื™ื–ื•ืจ ื”ื’ื™ื“ื•ืœ ืœืื•ืจืš ืชืขืœืช ื‘ื™ื•ืคืกื™ื™ืช ืžื—ื˜ ื”ื™ื ืงื˜ื ื” )2.7%(. ื ื’ืขื™ื ืงื˜ื ื™ื ืžืก"ืž ืžื—ื™ื™ื‘ื™ื ืžืขืงื‘ ืฆืžื•ื“ ื‘ืขื–ืจืช ื“ื™ืžื•ืช. ื‘ื™ื•ืคืกื™ื” ืฉืœื™ืœื™ืช ืœืžืžืื™ืจื•ืช ืื™ื ื” ืฉื•ืœืœืช ืกืจื˜ืŸ, ื•ืœื›ืŸ ื ื“ืจืฉ ืžืขืงื‘ ืœืื•ืชื” ืงืฉืจื™ืช ื›ืœ 6-3 ื—ื•ื“ืฉื™ื ืขื“ ืœื”ื™ืขืœืžื•ืช ืื• ื”ื’ื“ืœื” ืื• ืขื“ ืฉื”ื™ื

ื”ื•ืคื›ืช ืœื˜ื™ืคื•ืกื™ืช ืœืก"ื›. Barcelona Clinic Liver(ื BCLC - ื”ืฉื™ื˜ื” ื”ืกืคืจื“ื™ืช ืžื‘ืจืฆืœื•ื ื”Cancer(, ื”ื™ื ื”ื™ื•ื ื”ืฉื™ื˜ื” ื”ืžืงื•ื‘ืœืช ืœื”ืขืจื›ืช ื˜ื™ืคื•ืœ ืžื•ื ื—ื” ืฉืœื‘

ืกืจื˜ืŸ ื›ื‘ื“ ืจืืฉื•ื ื™ืจื™ืคืขืช ืกืคื“ื™

ื”ื™ื—ื™ื“ื” ืœืžื—ืœื•ืช ื›ื‘ื“, ื‘ื™ื”"ื— ื”ื“ืกื” ื•ื‘ื™ืช ื”ืกืคืจ ืœืจืคื•ืื” ืฉืœ ื”ื“ืกื” ื•ื”ืื•ื ื™ื‘ืจืกื™ื˜ื” ื”ืขื‘ืจื™ืช, ื™ืจื•ืฉืœื™ื

ื”ื™ืืจืขื•ืช ืก"ื› ื‘ืืจืฆื•ืช ื”ื‘ืจื™ืช ืขืœืชื” ื‘ืฉื ื™ ื”ืขืฉื•ืจื™ื ื”ืื—ืจื•ื ื™ื, ืืš ื”ืžืžื•ืฆืข ืฉืœ ื”ื™ืฉืจื“ื•ืช ืœโ€“5 ืฉื ื™ื ื ื•ืชืจ ื ืžื•ืš ืžโ€“12%

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Effective viral suppression1,2 + high genetic barrier1,2

Treatment for Chronic Hepatits B

Indication: Baraclude is indicated for the treatment of chronic HBV in adults with compensated liver disease and evidence of active viral replication and persistently elevated ALT levels. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions: dosage adjustment is recommended for patients with renal impairment, possible acute exacerbation of hepatitis, a higher rate of serious hepatic adverse events has been observed in patients with decompensated cirrhosis, occurrences of lactic acidosis (in the absence of hypoxaemia), sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues, patients should be advised that therapy with entecavir has not been proven to reduce the risk of transmission of HBV and therefore appropriate precautions should still be taken, this medicinal product contains lactose. There are no adequate data from the use of entecavir in pregnant women.

References: 1. Baraclude (entecavir) MOH approved physician prescribing leaet, June 2009 2. Tenney DJ et al. Hepatology (2009) Vol 49, 1-12

Biotis Ltd. 22 Hamelacha St. P.O.Box 11372, Rosh Haโ€™Ayin, 48091 Tel: 03-9002050 Fax: 03-9002029 www.biotis.co.ilBiotis is an exclusive representative of selected brands of BMS

Please refer to Baraclude approved Israeli Ministry of Health Physician Prescribing Information

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1343 - Modaha baraclude 21x27_25x19.ai 1 2/10/11 3:29 PM

Page 36: israel journal of the liver and related sciences

ื›ืชื‘ ื”ืขืช ืฉืœ ื”ื—ื‘ืจื” ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“ืžืจืฅ 2012 | ืžื‘ื™ืช ื”ื”ืกืชื“ืจื•ืช ื”ืจืคื•ืื™ืช ื‘ื™ืฉืจืืœ

ืžื—ืœืช ื•ื™ืœืกื•ืŸ: ืืกืคืงื˜ื™ื ื’ื ื˜ื™ื™ื ื‘ื™ืฉืจืืœ

ืกืจื˜ืŸ ื›ื‘ื“ ืจืืฉื•ื ื™-

For first choice treatment of bleeding oesophageal varices - the only therapy that IMPROVES SURVIVAL *

References: 1. Bosch et al. Seminars in Liver Disease 2008;28;3-25 2. Bosch J et al. Journal of Hepatology; 48 (2008); s68-s923. Cardenas A. Clin Liver Dis 14 (2010) 251-2624. Doctor's leaflet June 2010

*Approved indication: Bleeding oesophageal varices and treatment of type I hepatorenal syndrome

Ferring Pharmaceuticals Ltd. P.O.Box 3551, Caesarea Industrial Park 38900, IsraelTel.:+972-4-6309500 Fax: +972-4-6309511www.ferring.com

ืชืงืฆื™ืจื™ ื”ื›ื ืก ืฉืœ ื”ื—ื‘ืจื”ื”ื™ืฉืจืืœื™ืช ืœื—ืงืจ ื”ื›ื‘ื“

ืฉื™ื™ืขืจืš ื‘ื›ืคืจ ื‘ืœื•ืื‘ึพ17-15 ืœืžืจืฅ 2012

C ื”ื˜ื™ืคื•ืœ ื‘ื“ืœืงืช ื›ื‘ื“ ื ื’ื™ืคื™ืช ืžืกื•ื’