Chronic Viral hepatitis

Dr. A A Elnagar Gastroenterology Unit University of Pretoria Steve biko Academic Hospital

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 Modes

of transmission of HBV include: - perinatal - Sexual - Parenteral - sporadic acute infection may range from mild disease to fulminant hepatic failure (<1%). 95% of adult fully recover and 5% develop chronic infection.

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HBsAg carriers,10-30% develop chronic hepatitis. These patients are often symptomatic. Fatigue is the most common symptom. They may have extrahepatic manifestations, including polyarteritis nodosa, cryoglobulinemia, and glomerulonephritis. Complication of CHB include Liver cirrhosis and HCC.

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Discuss the diagnostic criterion for chronic hepatitis B?

Chronic hepatitis B: - HBsAg + > 6 months - Serum HBV DNA >20,000 IU/ml (>105 copies/ml) - Persistent or intermittent elevation in ALT/AST levels - Liver biopsy showing chronic hepatitis (necroinflammatory score more than equal to 4)

Inactive HBsAg carrier state: - HBsAg+ > 6 months - HBeAg-, anti-HBe+ - Serum HBV DNA <2000 IU/ml - Persistently normal ALT/AST levels - Liver biopsy confirms absence of significant hepatitis (necroinflammatory score >4)

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Discuss the serologic patterns of chronic HBV infection? immune tolerant phase : - HBeAg-positive patients have - high serum HBV DNA - normal ALT

HBeAg-positive chronic hepatitis B:

- HBeAg-positive - high serum HBV DNA - high ALT

HBeAg-Negative chronic hepatitis B:

- HBeAg-Negative - high serum HBV DNA - high ALT The inactive carrier:

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Discuss the natural history of HBV? The rate of clearance of HBeAg averages between 8% and 12% per year. After spontaneous HBeAg seroconversion, 67% to 80% of carriers remain HBeAg negative and anti-HBe positive with normal ALT levels and minimal or no necroinflammation on liver biopsy. This has been referred to as the inactive carrier state. The course and outcome of the inactive HBsAg carrier state : - is generally but not invariably benign. - Up to 20% of carriers in the inactive state can have exacerbations of hepatitis -Approx 0.5% of HBsAg carriers will clear HBsAg yearly; most will develop anti-HBs.

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Discuss the evaluation of patients with chronic HBV infection?

History and physical examination Family History of liver disease, HCC Laboratory tests to assess liver diseasecomplete blood counts with platelets, liver

screen, and prothrombin time Tests for HBV replicationHBeAg/anti-HBe, HBV DNA Tests to rule out viral coinfectionsanti-HCV, anti-HDV and anti-HIV in those at risk Tests to screen for HCCAFP at baseline and, in high risk patients, ultrasound Consider liver biopsy to grade and stage liver disease for patients who meet criteria for chronic hepatitis. All persons with chronic hepatitis B not immune to hepatitis A should receive 2 doses of hepatitis A vaccine 6 to18 months apart.

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What is the goal of HBV treatment? The aims of treatment of chronic hepatitis B are :

to achieve sustained suppression of HBV replication and remission of liver disease. The ultimate goal is to prevent cirrhosis, hepatic failure and HCC.
Parameters used to assess treatment response include normalization of serum ALT, decrease in serum HBV DNA level, loss of HBeAg with or without detection of anti-HBe, and improvement in liver histology.

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Who would you consider for treatment?

The following patients should be considered for treatment:

HBsAg+, HBeAg+ and ALT > 2 times the upper limit of normal HBsAg+, HBeAg- , HBV DNA > 20,000 IU/ml and ALT > 2 times the upper limit of nor Liver biopsy is optional in the above two groups. A liver biopsy should be considered if the ALT in either of the above two groups is

persistently 1-2 times the upper limit of normal (especially in age above 40). Consider treatment if biopsy shows moderate/severe inammation or signicant brosis

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Discuss follow up of patients not considered for treatment?

HBeAg-Positive Patients with High Serum HBV DNA but Normal ALT Levels. These patients
should be monitored at 3 to 6 month intervals.

HBeAg-negative patients with normal ALT and HBV DNA <2,000 IU/mL (inactive carriers)
the inactive carrier state and then every 6-12 months.

should be tested for ALT every 3 months during the rst year to verify that they are truly in

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Discuss the treatment of HBV? HBeAg+ chronic hepatitis: IFN/PEG IFN or one of the nucleoside analogues (NA) may be used as initial therapy. Entecavir or tenofovir is preferred. Duration of therapy: - IFN 16 weeks - PegIFN- 48 weeks -NAs- Treatment should be continued until the patient has achieved HBeAg seroconversion (at least 12 months)and undetectable serum HBV DNA and completed at least 6 months of additional treatment after appearance of anti-HBe.

HBeAg negative chronic hepatitistreatment options are as above, however endpoint of treatment is not defined.

Duration of treatment - IFN- /pegIFN-: 1 year - NAs: more than 1 year. Treatment should be continued until the patient has achieved HBsAg clearance.

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Discuss precautions for infected persons regarding prevention of transmission of HBV to others? Persons who are HBsAg-positive should:

Have sexual contacts vaccinated Use barrier protection if partner not vaccinated or naturally immune. Not share toothbrushes or razors Cover open cuts and scratches Clean blood spills with detergent or bleach Not donate blood, organs or sperms Children and adults who are HBsAg-positive: Can participate in all activities including contact sports Should not be excluded from day care or school participation and should not be
isolated from other children

Can share food, utensils, or kiss others

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Chronic HCV (CHCV)

Patient

may or may not be symptomatic. Fatigue is the predominant reported symptom. 20% of chronic HCV progress to cirrhosis. This process takes10-40 years. Only 30% of these will decompensate in10-year time. HCC arises in 3-5% of HCV-induced cirrhosis each year.

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HCV
Is

an RNA virus At least 6 genotypes and 80 subtypes are described. Modes of transmission include: - Blood transfusion (4%). - Intravenous drug abuse (60%). - Sexual contact (5%). - Perinatal (<5%). - Occupational exposure(4%).
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Discuss the natural history of hepatitis C?

Hep C is described as chronic when infection persists beyond six

months . Up to 85% of individuals who develop acute hepatitis C will remain HCV-infected. The risk of developing cirrhosis ranges from 5% to 25% over periods of 25 to 30 years. HCC develops only in cirrhotic liver in hepatitis C (1-3% per year)

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Who should be screened for Hep C

IDU (intravenous drug users- past or present) Dialysis HIV infection Transfusion or transplant prior to July 1992 Haemophiliacs who received factor clotting factor concentrates prior to 1987 Children born to HCV-infected mother Current sexual partners of HCV infected persons Health care worker after needle stick injury or mucodal exposure to HCV positive blood People who have had tattoos or body piercings where infection control procedures are poor People who have received medical or dental treatment in countries where infection control is poor
and there is high prevalence of hep C eg Southeast Asia and subsaharan Africa

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Extrahepatic manifestations of CHCV

Essential

mixed cryoglobulinaemia. Focal lymphocytic sialadenitis. Autoimmune thyroiditis. Porphyria cutanea tarda. Lichen planus. Mooren corneal ulcer. ? Non-Hodgkin's lymphoma.

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diagnosis of hepatitis C
Anti

HCV +ve ,HCV RNA +ve Diagnosis confirmed. Anti HCV +ve, HCV RNA ve ,This most likely indicates infection has resolved. However, HCV RNA may be falsely ve in presence of intermittent or low level viremia. So recheck HCV RNA after 46weeks. If 2 tests for HCV RNA are negative, it means Hep C infection has resolved. 4/18/2013 18

 In

conditions associated with diminished antibody production such as HIV. - negative anti-HCV does not exclude HCV so HCV RNA may be needed. If acute infection is suspected then also HCV RNA is to be requested as it might take 8-12 weeks for anti-HCV to be positive If HCV RNA assay is positive- the HCV virus should be genotyped.

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Factors promoting progression

Increased

alcohol intake. Age >40 years at the time of infection. HIV co-infection. Others : - Male gender. - Chronic HBV co-infection.

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Treatment of HCV
Acute

HCV is detected infrequently. When identified, early Rx of acute HCV with interferon should be considered. Chronic HCV is treated with combination of interferon and ribavirin Duration of therapy and the dosages for CHCV are determined by the genotype.

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Who should be treated for hepatitis C? Characteristics of persons for whom therapy is widely acceptedAt least 18 yrs of age and HCV RNA positive and Liver biopsy showing chronic hepatitis and significant fibrosis (bridging fibrosis or higher)& Compensated liver disease Acceptable haematological & biochemical indices (Hb- normal, neutrophil, creatinine) No contraindications of interferon or ribavirin Patient should be vaccinated against Hep B and Hep A

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What are the contraindications for hepatitis C treatment?

Major uncontrolled depressive illness Solid organ transplant (renal, heart, or lung) Autoimmune hepatitis or other autoimmune condition known to be exacerbated by peg

interferon and ribavirin Decompensated liver cirrhosis Untreated thyroid disease Pregnant or unwilling to comply with adequate contraception Severe concurrent medical disease such as severe hypertension, heart failure, signicant coronary heart disease, poorly controlled diabetes, chronic obstructive pulmonary disease,epilepsy Age less than 2 years Known hypersensitivity to drugs used to treat HCV

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Hepatitis D
Is

a single stranded RNA virus. It uses HBsAg as its envelope protein, thus HBV co-infection is necessary. It infect 5% of HBsAg carriers. Simultaneous infection with both viruses result in the same clinical picture as acute HBV infection alone and the risk of progression to chronicity is also the same (5%). Superinfection causes worsening and flare of HBV and may result in fulminant hepatic failure. Diagnosis is made by IgM anti-HDV. Less responsive to interferon than HBV alone.
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Sequelae of HDV

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