savary-miller grade 1: unconfluent eritematous erosions,one or more grade 2: multiple confluent,...
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CLASSIFICATION OF ESOPHAGITIS
SAVARY-MILLER
Grade 1: unconfluent eritematous erosions,one or more
Grade 2: multiple confluent, uncircumferenceal erosions
Grade 3: confluent,circumferenceal erosions of esophagus
Grade 4: complications:ulcer,stenosis,Barrett metaplasia
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LOS ANGELES CLASSIFICATION OF ESOPHAGITIS
A. One or more erosions, lenght less than 5 mm
B. At least one erosion longer than 5 mm, but unconfluent
C. One or more erosions extended between 3/4 mucosa folds, uncircumferenceal
D . Circumferenceal erosions
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HEPATITIS C INFECTIONEPIDEMIOLOGY
More than 150milion people worldwide are infected with hepatitis C virus(HCV),an RNA virus of the flavivirus family.
Transmision mainly through injection-drug use(>60% of cases in UK) or blood-product transfusion(eliminated due to screening of donated blood).
Skin piercing procedures ,transmission in monogamous heterosexual relationships <6%.
Mother to infant transmission occurs in 5% of cases,increased in 18% if mother co-infected with HIV.
Breastfeeding transmission is not reported .
6 main HCV genotypes 1,2,3 in Europe,USA, 4 in Egypt,Middle East subtypes a-c.
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CLINICAL FEATURESLess than 15% of patients develop acute icteric hepatitisChronic infection in 50-85% of cases,as defined by
persistence of HCV RNA in the serum,usually clinically silent ,with liver damage occuring over many years.
<20% will develop severe fibrosis/cirrhosis after 20 years of infection in the absence of cofactors(alcohol).
Risk factors for disease progression:high circulating virus level,long duration of disease,older age at acquisition,male sex,alcohol excess,co-infection with HIV/hepatitis B.
4% of patients per year with HCV cirrhosis develop HCC.Non-specific complaints:fatigue,headache ,poor
concentration
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EXTRAHEPATIC ASSOCIATIONS OF HEPATITIS C
Cryoglobulinaemia in 35-55% of chronic patients -most patients are asymptomatic - pruritus and arthralgia in 18% -neuropathy and membranous glomerulonephritis in
2%Lichen planusAutoimune hepatitisThyroiditisPolymyositisPolyarteritis nodosumPorphyria cutanea tardaSjogren’s syndrome
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INVESTIGATIONSAnti-HCV antibody.ELISA test +(RIBA)confirms
exposure to HCV,but no persistence of infection.HCV RNA by PCR confirms ongoing infection,with cut-off
variable,usually 100-1000 viral copies/ml.HCV genotype is essential to be determined in patients
considered for treatment,as influences treatment response.Liver function tests.ALT/AST elevated,1.5-2.5 UL,but
fluctuations are common with poor correlation between the level of viraemia or severity of histological findings.
Liver biopsy-invasive method of assessing the degree of inflammation and fibrosis;should be considered in all HCV RNA+patients,if AST/ALT abnormal.
FIBROSCAN,FIBROMAX-non-invasive methods
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INVESTIGATIONSAdditional blood tests.ASM antibodies-
autoimune hepatitis association which can be exacerbated by antiviral therapy.
Thyroid function testsHBs Ag for chronic hepatitis B,more
progressive histological disease in those with HCV.
HIV testingAbdominal US to identify features of cirrhosis
and portal hypertension;repeat 6 monthly+ AFP in patients with proven cirrhosis-risk of HCC !
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MANAGEMENTProgression usually seen in those who drink
excess alcohol!Vaccinate against hepatitis A and B ,as co-
infection may lead to disease progression,or fulminant liver failure.
Patients should be advised not to donate blood ,the risk of shared needles by drug users
Avoid sharing razors and toothbrushesSexual transmission,condoms should be used
during casual sexual contacts
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ANTIVIRAL TREATMENT Indicated in a patient with positive anti-HCV antibody, + HCV-RNA,raised liver enzymes(ALT,AST) and moderate to severe
hepatitis on liver biopsy, FIBROSCAN/FIBROMAX (non-invasive explorations).
Long-acting pegylated-alpha Interferon(PEG IFN 180microgr./weekly)+RIBAVIRIN 1000-1200mg/day(>75kg) ,12 months is the treatment of choice.
‘’Gold standard’’for assesssing treatment response is sustained virological response(SVR),defined as negative HCV RNA 6 months after completing treatment.
Genotype 1 is less responsive,with 45-55% SVR,genotype 2/3 gives SVR of 80% on 6 months course,even 4 if HCV-RNA is negative at 6 weeks.
End-stage liver disease due to chronic hepatitis is the commonest indication for liver transplantation.
Recurrence of HCV in the grafted liver is almost universal,with cirrhosis occurring at an accelerated rate in these immunocompromised patients.
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SIDE-EFFECTS OF HC TREATMENTInfluenza-like symptomsNauseaWeight lossAutoimmune reactionsDepressionLethargyHypersensitivityMyelosuppressionHypo/hyperthyroidismHair loss
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PREDICTORS OF LONG-TERM RESPONSE TO IFN
Non-viral genotype 1Low pre-treatment viraemiaNegative HCV-RNA after 1 month of
treatmentYounger ageNon-black racial originAbsence of cirrhosis on biopsyALT normalized in first 12 weeks of treatmentFemaleLow hepatic iron stores
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TRIPLE THERAPY IN HCVBOCEPREVIR-proteaze inhibitor (PI),enzyme CYP3A4/5IFN+RBV+BCV-at relapsers,non-responders,genotype
1; 3 adm.each 7-9 hours,over 4 weeks of
doubletherapy(,,Lead-in T’’),after meals.Side effects: anemia,disgeuziaEritropoetine(EPO),expansive and hard to find !TELAPREVIR-PI-3 adm.each 8 hours, greasy meals,with
IFN+RBV ,12 weeks,than only double therapy,36 weeks .
Side effects: Cutaneous reactions (dermatologist consult),abdominal pain,diarrhea.
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HEPATITIS BRoute of transmission is perinatally(90%
infection rate in infants born to HBeAg+ve mothers)
Blood inoculation through unclean needles remains important
Sexual transmission accounts for 30% of infections in developed countries
More than 300 milion people worldwide are infected with HVB chronic infection , 2% in Western Europe and USA,20% in areas of Southeast Asia.
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CLINICAL FEATURESAge at infection strongly determines
chronicity,reflecting host imunity (>90% in neonates, 20-50% 1-5 years , <5% in adults).
Highest rate of complications in highly replicating disease (HBe Ag+,precore mutant infection )
Spontaneous clearance of infection (Hbs Ag-ve occurs in 1% of chronic infected patients/year).
Fatigue,weakness,discomfort in the right upper quadrant,weight loss,in compensated disease.
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INVESTIGATIONSHBV serology:HBsAg indicates ongoing infection;HBe Ag confirms high viral replication ,may be
negative in HBe-ve chronic HB, anti-HBc IgM(acute infection); anti-HBc IgG-previous or ongoing infection
Anti-HBs-resolved infection or vaccinatedHBV DNA by PCRLiver function tests: ALT/ASTAFP perform 6 monthly with liver
ultrasound,especially in cirrhotics-HCC risk !Liver biopsy,Fibroscan,Fibromax when treatment is
consideredHIV testing
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MANAGEMENTUsual goal of treatment is to supress HBV replication,induce
HBeAg seroconversion(clearance of HBeAg ;appearance of anti-HBe) and reduce liver injury.
Ultimate goal is to clear HBsAg and prevent cirrhosis and HCC.Treatment is indicated for those with replicative disease
(HBe+ve,pre-core infection)and hepatic damage.PEG IFN alpha 6 months induces HBeAg seroconversion in 30%
at 1 year course of treatment.Lamivudine 100 mg/day in naive patients,induces HBeAg
seroconversion in 25% after one year of use,56% at 3 years,but treatment-resistant may develop in >40% after 3 years of use.
LV+PEG IFN ,no additional benefit.LV use to be drug of choice in patients with decompensated
cirrhosis and prior to liver transplantation ,to control replication.
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NUCLEOTIDE ANALOGUESENTECAVIR5mg/day in naive patients,unlimited administration10mg/day in those who didn’t respond to other
treatmentADEFOVIRTENOFOVIRHepatitis B vaccination:passive immunization with HBIG,0.1 ml/kg
body weight after exposure or birth to chronically infected mother and active immunization,10-20mcg HBsAg given at 0,1,6 months.