chronic hepatitis c & d

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.,



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



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



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



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



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



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



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



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



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



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



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



LONG TERM MAINTENANCE THERAPY

RECOMMENDED

1.cutaneous vasculitis

2.glomerulonephritis

LONG TERM MAINTENANCE THERAPY

ASSESSED IN CLINICAL TRIALS1.relapsers

2.nonresponders



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



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



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



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



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



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



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



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



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



THANK U

chronic hepatitis c & d

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