11. chronic hepatitis

CHRONIC HEPATITIS CHRONIC HEPATITIS

The contours of the liver and spleen as wellas the gall bladder in the right and left

hypochondrium

THE ANATOMY

OF THE PORTAL VENOUS SYSTEM

CHRONIC CHRONIC HEPATITISHEPATITIS

CHRONIC HEPATITISCHRONIC HEPATITISDefinitionDefinition

Chronic hepatitis is a broad clinical and Chronic hepatitis is a broad clinical and pathologic syndrome that encompasses an pathologic syndrome that encompasses an etiologically diverse group of diseases etiologically diverse group of diseases characterized by long-term elevation of liver characterized by long-term elevation of liver chemistries and the finding of hepatic chemistries and the finding of hepatic inflammation on liver biopsy.inflammation on liver biopsy.

Chronic hepatitis is generally defined Chronic hepatitis is generally defined as disease that has lasted as disease that has lasted for 6 monthsfor 6 months or longer or longer

Anxiety Anxiety Arthritis Arthritis Ascites (swelling in the stomach area) Ascites (swelling in the stomach area) Blurred Vision Blurred Vision Chills Chills Dark Urine Dark Urine Decline in sex drive Decline in sex drive Depression Depression Dizziness Dizziness Dry Skin Dry Skin Edema (swelling of the hands, feet & Edema (swelling of the hands, feet &

legs) legs) Excessive Bleeding Excessive Bleeding Excessive gas Excessive gas Eye or eyesight problems (blurred Eye or eyesight problems (blurred

vision or dry eyes) vision or dry eyes) Fatigue Fatigue Fever Fever Flu-like symptoms Flu-like symptoms Gallstones Gallstones Gray, yellow, white or light colored Gray, yellow, white or light colored

stools stools Headaches Headaches Hepatalgia (pain or discomfort in liver Hepatalgia (pain or discomfort in liver

area) area) Hot flashes Hot flashes Indigestion Indigestion

Inflammation in the joints Inflammation in the joints Insomnia Insomnia Irritability Irritability Itching Itching Jaundice (yellowing of eyes and/or Jaundice (yellowing of eyes and/or

skin) skin) Joint pain Joint pain Mood changes or swings Mood changes or swings Memory loss, mental confusion Memory loss, mental confusion Menstrual problems Menstrual problems Muscle aches Muscle aches Nausea Nausea Rashes/Red spots Rashes/Red spots Red palms Red palms Sensitivity to heat or cold Sensitivity to heat or cold Sleep disturbances Sleep disturbances Slow healing and recovery Slow healing and recovery Susceptibility to illness/flu Susceptibility to illness/flu Sweating Sweating Vertigo Vertigo Vomiting Vomiting Water retention Water retention Weakness Weakness Weight gain Weight gain Weight loss Weight loss

CYTOLYTIC SYNDROMECYTOLYTIC SYNDROME

alanine aminotransferase increased, alanine aminotransferase increased, aspartate aminotransferase increasedaspartate aminotransferase increased Increased LDHIncreased LDH Increased ferritinIncreased ferritin HyperbilirubiemiaHyperbilirubiemia

CCholestasis holestasis abdominal mass (e.g. cancer)abdominal mass (e.g. cancer) biliary atresia and other pediatric biliary atresia and other pediatric

liver diseasesliver diseases biliary traumabiliary trauma congenital anomalies of the biliary congenital anomalies of the biliary

tracttract gallstonesgallstones intrahepatic cholestasis of intrahepatic cholestasis of

pregnancy (obstetric cholestasis)pregnancy (obstetric cholestasis) primary biliary cirrhosis, an primary biliary cirrhosis, an

autoimmune disorderautoimmune disorder primary sclerosing cholangitis, primary sclerosing cholangitis,

associated with inflammatory associated with inflammatory bowel diseasebowel disease

some drugs, (e.g. flucloxacillin and some drugs, (e.g. flucloxacillin and erythromycin)erythromycin)

ABCC2 gene polymorphismABCC2 gene polymorphism

Alkaline phosphatase Alkaline phosphatase elevations of serum bile acid elevations of serum bile acid

levelslevels elevated levels of Gamma elevated levels of Gamma

Glutamyl Transferase [GGT]Glutamyl Transferase [GGT]

itchiness (pruritus). Pruritus is the itchiness (pruritus). Pruritus is the primary symptom of cholestasis primary symptom of cholestasis

jaundice. jaundice. pale stool. This symptom implies pale stool. This symptom implies

obstructive cholestasis.obstructive cholestasis. dark urinedark urine

Bile is secreted by the liver to aid Bile is secreted by the liver to aid in the digestion of fats. Drugs such in the digestion of fats. Drugs such as gold salts, nitrofurantoin, as gold salts, nitrofurantoin, anabolic steroids, chlorpromazine, anabolic steroids, chlorpromazine, prochlorperazine, sulindac, prochlorperazine, sulindac, cimetidine, erythromycin, estrogen cimetidine, erythromycin, estrogen can cause cholestasis and may can cause cholestasis and may result in damage to the liver.result in damage to the liver.

hepatocellular insufficiencyhepatocellular insufficiency

AlbuminAlbumin TransferrineTransferrine ChplesterolChplesterol protro,mbineprotro,mbine CholinesterasaCholinesterasa ΑΑ-lipoproteins-lipoproteins HyperbilirubinemiaHyperbilirubinemia

Mesenchymal inflammation Mesenchymal inflammation

Hyper-Hyper-γγ globulinemia globulinemia CRPCRP ESRESR

CHRONIC HEPATITIS CHRONIC HEPATITIS CLASSIFICATION CLASSIFICATION

CChronic hronic VViral iral HHepatitis epatitis BB CChronic hronic VViral iral HHepatitis epatitis CC CChronic hronic VViral iral HHepatitis epatitis DD CChronic hronic VViral iral HHepatitis epatitis nonidentificatednonidentificated Autoimmune Autoimmune HHepatitisepatitis (type 1, 2 ,3) (type 1, 2 ,3) Toxic HToxic Hepatitisepatitis, , Drug-Induced HepatitisDrug-Induced Hepatitis CCryptogenic ryptogenic HHepatitisepatitis Alcoholic HAlcoholic Hepatitisepatitis Metabolic HMetabolic Hepatitisepatitis Cholestatic HCholestatic Hepatitisepatitis Nonspecific Reactive HNonspecific Reactive Hepatitisepatitis

Grades of Inflammationand Stages of Fibrosis on Liver

Biopsies

CHRONIC HEPATITIS CHRONIC HEPATITIS CLASSIFICATIONCLASSIFICATION

ACCORDING TO SEVERITY ACCORDING TO SEVERITY (level of (level of Aminotransferases))

A C T I V ITYA C T I V ITY

MILD MODERATE SEVERE

CHRONIC HEPATITISCHRONIC HEPATITISCOMPLICATIONSCOMPLICATIONS

HEPATIC ENCEPHALOPATHY HEPATIC ENCEPHALOPATHY VVARICEAL BLEEDINGARICEAL BLEEDING ASCITESASCITES GLOMERULONEPHRITISGLOMERULONEPHRITIS OTHERSOTHERS

CHRONIC HEPATITIS CHRONIC HEPATITIS CLASSIFICATION CLASSIFICATION

CCHRONIC HRONIC VVIRAL IRAL HHEPATITIS EPATITIS BB CCHRONIC HRONIC VVIRAL IRAL HHEPATITIS EPATITIS CC CCHRONIC HRONIC VVIRAL IRAL HHEPATITIS EPATITIS DD CCHRONIC HRONIC VVIRAL IRAL HHEPATITIS EPATITIS

NONIDENTIFICATEDNONIDENTIFICATED Autoimmune Autoimmune HHepatitisepatitis (type 1, 2 ,3) (type 1, 2 ,3) Toxic HToxic Hepatitisepatitis, , Drug-Induced HepatitisDrug-Induced Hepatitis CCryptogenic ryptogenic HHepatitisepatitis Alcoholic HAlcoholic Hepatitisepatitis Metabolic HMetabolic Hepatitisepatitis Cholestatic HCholestatic Hepatitisepatitis Nonspecific Reactive HNonspecific Reactive Hepatitisepatitis

General ConceptsGeneral Concepts

Hepatitis = 'inflammation of the liver'.Hepatitis = 'inflammation of the liver'. six medically important viruses are commonly six medically important viruses are commonly

described as “hepatitis viruses”:described as “hepatitis viruses”:

HAV,HBV,HCV,HDV,HEV,HGVHAV,HBV,HCV,HDV,HEV,HGV. .

AA“ Infectious”

“ Serum”

Viral hepatitis

Entericallytransmitted

Parenterallytransmitted

F, G, TTV? other

EE

NANBNANB

BB DD CC

Viral Hepatitis - Historical Perspectives

Table 24.12Table 24.12

CHRONIC VCHRONIC VIRALIRAL HEPATITISHEPATITIS

5 5 to to 10% 10% of cases of hepatitis of cases of hepatitis В В (with or (with or without hepatitis D virus co-infection)without hepatitis D virus co-infection)

and about and about 75% 75% of cases of hepatitis C of cases of hepatitis C become chronic. become chronic.

Infection with hepatitis A virus or Infection with hepatitis A virus or hepatitis E virus is not a cause of hepatitis E virus is not a cause of Chronic HepatitisChronic Hepatitis. .

HBVHBV : Structure: Structure

HBV Structure & Antigens Dane Dane particleparticle

HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr)HBcAg = inner core protein (a single serotype) HBeAg = secreted protein; function unknown

Possible Outcomes of HBV InfectionPossible Outcomes of HBV Infection

Acute hepatitis B infection

Chronic HBV infection

3-5% of adult-acquired infections

95% of infant-acquired infections

Cirrhosis

Chronic hepatitis

12-25% in 5 years

Liver failure Hepatocellular carcinoma

Liver transplant

6-15% in 5 years 20-23% in 5 years

DeathDeath

77 、、 Laboratory DiagnosisLaboratory Diagnosis

CHRONIC VCHRONIC VIRALIRAL HEPATITISHEPATITIS

Hepatitis B virus and hepatitis C virus are the major causes of chronic hepatitis in the world.

Approximately 80% of individuals infected with HCV will become chronic carriers, of whom a majority will develop a degree of liver damage ranging from fatty liver to cirrhosis.

Chronic HBV and HCV infection predispose patients to developing hepatocellular carcinoma.

CHRONIC HEPATITIS CHRONIC HEPATITIS CLASSIFICATION CLASSIFICATION

CChronic hronic VViral iral HHepatitis epatitis BB CChronic hronic VViral iral HHepatitis epatitis CC CChronic hronic VViral iral HHepatitis epatitis DD CChronic hronic VViral iral HHepatitis epatitis nonidentificatednonidentificated AUTOIMMUNE AUTOIMMUNE HHEPATITISEPATITIS (TYPE 1, 2 ,3) (TYPE 1, 2 ,3) Toxic HToxic Hepatitisepatitis, , Drug-Induced HepatitisDrug-Induced Hepatitis CCryptogenic ryptogenic HHepatitisepatitis Alcoholic HAlcoholic Hepatitisepatitis Metabolic HMetabolic Hepatitisepatitis Cholestatic H Cholestatic Hepatitisepatitis Nonspecific Reactive HNonspecific Reactive Hepatitisepatitis

AUTOIMMUNE HEPATITIS Autoimmune hepatitis is four times more common in

women than in men, and is most aggressive when it presents in the third

and fourth decades. AIH can be associated with other autoimmune

diseases. Important differential diagnoses include viral

hepatitis, Wilson's disease and drug reactions. There is a rise in IgG, a positive anti-smooth-muscle

antibody present in 60%, and antinuclear antibody and liver-kidney microsomal antibody (LKM-1) may be present.

Long-term immunosuppression is required with corticosteroids and often azathioprine. Response rate to therapy (corticosteroids) is 80-90%.

AUTOIMMUNE HEPATITIS

Patients with severe disease who are treated with corticosteroids have a 10-year survival rate of 60% to 70%,

whereas untreated patients have a survival rate of less than 30%.

CHRONIC HEPATITIS CHRONIC HEPATITIS CLASSIFICATION CLASSIFICATION

CChronic hronic VViral iral HHepatitis epatitis BB CChronic hronic VViral iral HHepatitis epatitis CC CChronic hronic VViral iral HHepatitis epatitis DD CChronic hronic VViral iral HHepatitis epatitis nonidentificatednonidentificated Autoimmune Autoimmune HHepatitisepatitis (type 1, 2 ,3) (type 1, 2 ,3) TOXIC HTOXIC HEPATITISEPATITIS, , DRUG-INDUCED DRUG-INDUCED

HEPATITISHEPATITIS CCryptogenic ryptogenic HHepatitisepatitis Alcoholic HAlcoholic Hepatitisepatitis Metabolic HMetabolic Hepatitisepatitis Cholestatic HCholestatic Hepatitisepatitis Nonspecific Reactive HNonspecific Reactive Hepatitisepatitis

DRUG-INDUCED CHRONIC DRUG-INDUCED CHRONIC HEPATITISHEPATITIS

Hepatotoxic drugsHepatotoxic drugs::

- Paracetamol- Isoniazid

- Oestrogens- Antibiotics

-Methotrexate-others

FATTY LIVER Fat droplets appear in the

cytoplasm of hepatocytes; they may appear a few days

after an alcohol binge, but are almost always present in heavy drinkers (> 80 g of alcohol per day for > 5 years).

Fatty liver may occur, however, with obesity, diabetes mellitus, starvation and chronic hepatitis C virus infection

Fatty Liver

ALCOHOLIC HALCOHOLIC HEPATITISEPATITIS Alcohol abuse is a massive international

problem which has huge resource implications both for the community as a whole and also for health care.

Alcohol is enjoyed by many and used safely by the majority of people who drink it.

Alcohol abuse may be denied or not recognized by individuals or their families and friends.

Alcohol damages not only the liver, but many other organs also.

Effects of alcohol abuse

ALCOHOLIC HALCOHOLIC HEPATITISEPATITIS Alcoholic liver disease may develop in Alcoholic liver disease may develop in

women after less alcohol consumptionwomen after less alcohol consumption than is necessary to cause than is necessary to cause hepatitis or hepatitis or cirrhosis in men.cirrhosis in men.

Daily alcoholDaily alcohol consumption of consumption of approximately 50 g for 10 to 15 years is approximately 50 g for 10 to 15 years is associated with alcoholic liver diseaseassociated with alcoholic liver disease in in women, whereas 80 gwomen, whereas 80 g is associatedis associated with with alcoholic cirrhosis in men. alcoholic cirrhosis in men.

ALCOHOLIC HALCOHOLIC HEPATITISEPATITIS Alcoholic hepatitisAlcoholic hepatitis

refers to the refers to the pathologic Mallorypathologic Mallory stain findings of stain findings of alcoholic hyalin alcoholic hyalin surrounded by surrounded by polymorphonuclepolymorphonuclearar cell cell inflammationinflammation

METABOLIC HMETABOLIC HEPATITISEPATITIS HEMOCHROMATOSISHEMOCHROMATOSIS:: Characterized Characterized

by excessive deposition of iron in liverby excessive deposition of iron in liver WILSON DISEASE:WILSON DISEASE: Characterized by Characterized by

excessive deposition of copper in liver excessive deposition of copper in liver (mostly in young patients)(mostly in young patients)

αα1-ANTITRYPSIN DEFICIENCY:1-ANTITRYPSIN DEFICIENCY: results results in cirrhosis and emphysemain cirrhosis and emphysema

CHRONIC HEPATITISCHRONIC HEPATITISDIAGNOSISDIAGNOSIS

LABORATORY SYNDROMESLABORATORY SYNDROMES:: CytoliticCytolitic syndrome ( syndrome (↑AST, ↑ALT, ↑GGT, ↑AST, ↑ALT, ↑GGT,

↑Bilirubin↑Bilirubin )) CholestaticCholestatic syndrome ( syndrome (↑conjugated Bilirubin, ↑conjugated Bilirubin,

↑↑Alkaline phosphatase, ↑GGT, ↑cholesterol)↑GGT, ↑cholesterol) Liver cellular insufficiency Liver cellular insufficiency syndrome (↓syndrome (↓Albumine,

↓↓prothrombin, ↓cholesterol, ↓fibrinogen)↓cholesterol, ↓fibrinogen) Mesenchyme-inflammatory Mesenchyme-inflammatory syndrome (↑ESR, syndrome (↑ESR,

(globulins, ↑timol test ↑Le, ↑C-react. protein)-globulins, ↑timol test ↑Le, ↑C-react. protein-الال↑↑ Hypersplenism Hypersplenism (anemia, thrombocytopenia, (anemia, thrombocytopenia,

leukocytopenia)leukocytopenia)

CHRONIC HEPATITISCHRONIC HEPATITISPLAN of INVESTIGATIONSPLAN of INVESTIGATIONS

Total blood count Biochemical analysis (Glucose, Bilirubin, ALT, AST,

GGT, Alkaline phosphatase, Albumin, الال-globulins, -globulins, Cholesterol, Cholesterol, Liver tests, Sodium, Potassium, Urea, Creatinine)

Urinanalysis, Diastase of urine Coagulogram Markers of VViral iral HHepatitis epatitis (chain polimerase reaction, (chain polimerase reaction,

immunoenzyme analysis)immunoenzyme analysis) ImmunogramImmunogram CoprogramCoprogram ECG Endoscopy USD, CT Needle liver biopsy

CCHRONIC HRONIC VVIRAL IRAL HHEPATITISEPATITIS TREATMENTTREATMENT

ANTIVIRAL THERAPY (Interferon therapy, Lamivudine therapy)

Corticosteroids are contraindicated, Corticosteroids are contraindicated, because viral replication is enhancedbecause viral replication is enhanced

INTERFERON THERAPY (Intron A, Velferon, Reaferon, Laferon)

CCHRONIC HRONIC VVIRALIRAL HHEPATITIS EPATITIS BB: :

5-105-10 millionmillion UnitsUnits 3 3 times times a aweekweek s/c or i/m s/c or i/m

for 3-for 3- 4-124-12monthsmonths

CCHRONIC HRONIC VVIRALIRAL HHEPATITIS EPATITIS CC:: 3-3-55 million unitsmillion units33 times a week times a week

for 12for 12-18-18 monthsmonths

CCHRONIC HRONIC VVIRAL IRAL HHEPATITIS EPATITIS DD:: 1010 million unitsmillion units33 times a week times a week

for 12for 12-18-18 monthsmonths

INTERFERON THERAPYSide effectsSide effects

influenzalike symptoms (fever, myalgia, influenzalike symptoms (fever, myalgia, arthralgia, and headache),arthralgia, and headache),

hematologic toxicity (granulocytopenia, hematologic toxicity (granulocytopenia, leukopenia, and thrombocytopenia), leukopenia, and thrombocytopenia),

systemic symptoms (fatigue and hair loss), systemic symptoms (fatigue and hair loss), neurologic signs (decreased neurologic signs (decreased

concentration, depression, and irritability),concentration, depression, and irritability), immune system disorders (development of immune system disorders (development of

autoantibodies, thyroid disease, or other autoantibodies, thyroid disease, or other autoimmune diseases)autoimmune diseases)

CONTRAINDICATIONS CONTRAINDICATIONS TO INTERFERON THERAPYTO INTERFERON THERAPY

hypersensitivity to interferon hypersensitivity to interferon

decompensated cirrhosisdecompensated cirrhosis immunosuppression associated with organ immunosuppression associated with organ

transplantation transplantation active autoimmune diseaseactive autoimmune disease significant psychiatric disease, including significant psychiatric disease, including

depression depression pregnancypregnancy

Autoimmune Autoimmune HHepatitisepatitisWeekWeek MonotherapyMonotherapy

Prednisolone,Prednisolone,mgmg

PrednisolonePrednisolone (mgmg) and Azathioprine (mg/kg) combination therapycombination therapy

Prednisolone Prednisolone Azathioprine

11 5050 5050 50-15050-15022 5050 4040 50-15050-15033 4040 3030 50-15050-150

44 3030 2020 50-15050-150

55 2525 1515 50-15050-150

66 2020 12,512,5 50-15050-150

7,87,8 1515 1010 50-15050-150

HEPATOPROTECTORSPlantPlant Carsil, Legalon, Carsil, Legalon,

Hepabene, Chofitol Hepabene, Chofitol Essential phospholipidsEssential phospholipids Essentiale, EnerlivEssentiale, Enerliv

AminoacidsAminoacids Glutargin, CitrargininGlutargin, Citrarginin

αα-- lipoic acid lipoic acid BerlithionBerlithion

Ursodezoxycholic acidUrsodezoxycholic acid Ursofalc, UrsosanUrsofalc, Ursosan

SyntheticSynthetic Thiotriazolin, AntralThiotriazolin, Antral

AnimalAnimal Vitohepat, SireparVitohepat, Sirepar

HomeopathicHomeopathic HalstenaHalstena

Thank you for attention!