Rolling review–the pathogenesis, diagnosis and management of viral hepatitis

SUMMARY Five major hepatotrophic viruses have been identified. The pathogenesis, diagnosis and treatment of chronic viral hepatitis continues to be intensely researched. Experimental evidence suggests that HLA restricted virus‐specific T cells play a role in hepatocellular injury in type A hepatitis. The absence of chronic infection indicates the effectiveness of the host immune response to hepatitis A virus (HAV). It is postulated that HAV may rarely trigger an autoimmune chronic hepatitis. Active prophylaxis of hepatitis A is possible. The elimination of hepatitis B is dependent on the recognition of viral determinants in association with HLA proteins on infected hepatocytes by cytotoxic T cells. The specific epitopes recognized by B and T cells are being mapped. Polymerase chain reaction (PCR) amplification and sequencing of genomic DNA in patients with chronic hepatitis B has indicated that nucleotide substitutions in the genome are not uncommon. Their pathogenicity is being explored. Antiviral therapy for hepatitis B remains difficult. Interferon is effective in a proportion of patients. Thymosin may prove to be more effective immunomodulatory therapy. New nucleoside analogues suppress HBV replication, but the safety of these drugs has been questioned after the appearance of severe liver toxicity with fialuridine. The data that hepatitis D virus is pathogenic has recently been challenged with the observation that HDV re‐occurs in transplanted liver after engrafting, but without signs of HBV recurrence or evidence of liver damage. Treatment of hepatitis D virus remains difficult. Several isolates of hepatitis C virus have been cloned, and the sequence divergence of these isolates indicates that there are several major genotypes and component subtypes of this polymorphic virus. Hypervariability of regions of the HCV envelope proteins may be important in persistence of HCV infection and immunopathogenesis. Type C hepatitis has a complex natural history, and several systemic manifestations as well as autoimmune disease have been linked to hepatitis C infection. Alpha interferon is beneficial in 25–30% of patients; certain genotypes may be more sensitive to interferon therapy. The hepatitis E virus causes acute, and in susceptible populations, fulminant hepatitis. The diagnosis can now be made with tests for anti‐HEV and Polymerase chain reaction. Other forms of viral hepatitis, particularly those associated with fulminant hepatitis, severe sporadic hepatitis and autoimmune disease are being sought.