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8/14/2019 Chronic Hepatitis c & d
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CHRONIC HEPATITIS C & D
SYMPOSIUM I MU
PROF.DR.A.AYYAPPAN,M.D.,
DR.GIRIDHAR BABU,M.D.,
DR.JERALD MAJELLAH,M.D..DR.SHEELA,M.D.,
DR.AMALRAJ,M.D.,
DR.GURUNAMASIVAYAM,M.D.,
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CHRONIC HEPATITIS
Defined as biochemical or histological
evidence of active ongoing hepatic inflammation
and necrosis persisting for more than 6 months.
Classification:
1.Chronic persistent hepatitis
2.Chronic active hepatitis
3.Chronic lobular hepatitis
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NEWER CLASSIFICATION
1.cause
2.histological activity or grade
3.degree of progression or stage
I.Causes of chronic hepatitis:
1.viral – HBV,HCV,HBV & HDV
2.autoimmune hepatitis
3.drug induced – INH,alpha methyldopa
4.occasionally wilson’s disease,alcoholic
hepatitis
5.cryptogenic
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II.HISTOLOGICAL ACTIVITY OR GRADE
1.histological activity index (HAI) –
modified by knodell ishak scoring system
2.Metavir scoring
Features assessed in HAI
1.periportal necrosis including piecemealnecrosis and bridging necrosis
2.intralobular necrosis (focal / confluent)
3.portal inflammation
A o - noneA 1 – mild
A 2 – moderate
A 3 – severe
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III.DEGREE OF PROGRESSION OR STAGE
Assessed by fibrosis
F o – no fibrosis
F 1 – portal fibrosis
F 2 – portal fibrosis with few or minimal bridging
fibrosis
F 3 – portal fibrosis with many bridging fibrosis
F 4 – cirrhosis
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CHRONIC HEPATITIS C
In 85% of cases
2o% progress to cirrhosis in 10 to 20 yrs
Risk of HCC – 1-4% per year after 30 yrs of infection
10 yr survival in 80% of pts with compensatedcirrhosis
Chronic HCV infection is very slowly and insidiously progressive
1/3 of the pts have normal ALT activity
30-50% have chronic hepatitis on liver biopsy
60% of pts remain asympyomatic and wellcompensated with no clinical sequelae of CLD
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CLINICAL MANIFESTATIONS
Fatigue is the most common symptom and is non specific
Jaundice is rare
Extra hepatic manifestations
1.mixed cryoglobulinemia(10-25%)
2.glomerulonephritis
3.porphyria cutanea tarda
4.cutaneous necrotising vasculitis
5.lichen planus
6.lymphoma
7.other auto immune disorders
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PATHOGENESIS
1.Direct cytopathic effect- obsolete
2.Host immune responses to HCV infected hepatocytes play amajor role in the pathogenesis
-CD 4+ helper T cells elaborate various cytokines and stimulate
HCV specific CD 8+ cytotoxic T cells-these act on the infected hepatocytes and limit the infectionand viral clearance
-failure of adequate immune responses result in chronicinfecton and hepatitis
3.Auto immunity – anti LKM 1 antibodies directed againstcyt.p450 2D6 enzyme
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DIAGNOSIS
1. Anti HCV antibodies
2. HCV RNA by PCR
3. Anti LKM 1 antibodies4. Liver biopsy to grade the necro inflammatory
activity and stage the fibrosis
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TREATMENT
Goals of treatment
1. Clearance of HCV RNA
2. Normalisation of liver enzymes
3. Normalisation of histology
SVR- sustained virological response
reduction of HCV RNA to undetectable level in serum by PCRafter 6 months of completion of therapy
EVR- early virological response
2-log 10 drop in HCV RNA level within the first 12 weeks oftherapy
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TREATMENT OPTIONS
1.Conventional IFN alpha
2.Pegylated IFN @ - PEG IFN @ 2a,
PEG IFN @ 2b3.PEG IFN @ & Ribavirin combination therapy
4.Liver transplantation for ESLD
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STANDARD INDICATIONS FOR THERAPY
1.detectable HCV RNA (with or without elevated ALT)
2.portal / bridging fibrosis or moderate to severe hepatitis on liver biopsy
THERAPY NOT RECOMMENDED ROUTINELY
1.children < 18 yrs
2.age > 6o yrs3.mild hepatitis on liver biopsy
THERAPY NOT RECOMMENDED
1.decompensated cirrhosis
2.pregnancy (teratogenicity of ribavirin)
RETREATMENT RECOMMENDED1.relapsers
2.nonresponders
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LONG TERM MAINTENANCE THERAPY
RECOMMENDED
1.cutaneous vasculitis
2.glomerulonephritis
LONG TERM MAINTENANCE THERAPY
ASSESSED IN CLINICAL TRIALS1.relapsers
2.nonresponders
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THERAPEUTIC REGIMENS
FOR HCV GENOTYPE 1 – 48 weeks
1.PEG IFN @ 2a 180 mic g weekly s.c
plusRibavirin 1000 mg/day (wt < 75 kg) to
1200 mg/day (wt > 75 kg) orally
2.PEG IFN @ 2b 1.5 mic g / kg weekly plus
Ribavirin 800 mg/ day
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FOR HCV GENOTYPE 2 & 3 – 24 weeks
1.PEG IFN @ 2a 180 mic g/ kg weekly
plus
Ribavirin 800 mg/day2.PEG IFN @ 2b 1.5 mic g / kg weekly
plus
Ribavirin 800 mg/day
for pts with advanced fibrosis and or high level HCVRNA level - 48 wks therapy
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FOR HCV-HIV COINFECTION
PEG IFN & Ribavirin combination therapy for
48 weeks irrespective of the genotype
Ribavirin dose- 600 to 800 mg/ day
1000 to 1200 mg/day if tolerated
Ribavirin may potentiate the toxicity of
Didanosine
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COMPLICATIONS OF IFN THERAPY
1.systemic flu-like symptoms
2.bone marrow suppression3.neuropsychiatric manifestations
4.autoimmune thyroiditis
5.alopecia,rashes,diarrhea andnumbness & tingling of the extremities
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COMPLICATIONS OF RIBAVIRIN THERAPY
1.Hemolytic anemia (15 – 30%)
2.Nasal and pulmonary congestion
3.Pruritus
4.Precipitation of gout
5.Teratogenicity
CONTRAINDICATIONS
1.Pregnancy
2.CRF
3.CAD/CVD
4.Hemoglobinopathies and severe anemia
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FACTORS ASSOCIATED WITH
REDUCED RESPONSIVENESS
1.Genotype 1
2.High level HCV RNA (>2 million copies/ml 0r > 800000 IU/ml)
3.Advanced fibrosis4.Long duration disease
5.Age > 40
6.Immunosuppression
7.Obesity and steatosis
8.Associated alcoholic liver disease
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CHRONIC HEPATITIS D
1.Incomplete RNA virus
2.Needs HBsAg of HBV as its outer envelope for replication andexpression
3.Either coinfection or superinfection
4.HDV coinfection has a good prognosis*80 – 90% of pts recover completely
*5 – 10% of pts develop fulminant
hepatic failure(as compared to <1% in HBV
infection)
5.HDV superinfection is associated with increased rate of progression to cirrhosis,decompensation and development ofHCC
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DIAGNOSIS
1.Anti HDV antibody
2.HDV RNA
3.Evidence of chronic HBV infection – HBsAg,IgG anti HBc Ab
4.Anti LKM 3 autoantibodies directed against
UDP glucuronyl transferase enzyme
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TREATMENT
1.IFN @ - at conventional dose
- reduce HDV RNA level and ALT
activity but has no impact on the
natural history2.High dose IFN @ - 9 million units 3 times a
week for 12 months
-improvement in 50% of pts
-beneficial effect for >15 yrs3.PEG IFN as an alternative therapy
4.Liver transplantation for ESLD
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THANK U