ROLLING REVIEW - THE PATHOGENESIS, DIAGNOSIS AND MANAGEMENT OF VIRAL-HEPATITIS

Five major hepatotrophic viruses have been identified. The pathogenesi s, diagnosis and treatment of chronic viral hepatitis continues to be intensely researched. Experimental evidence suggests that HLA restrict ed virus-specific T cells play a role in hepatocellular injury in type A hepatitis. The absence of chronic infection indicates the effective ness of the host immune response to hepatitis A virus (HAV). It is pos tulated that HAV may rarely trigger an autoimmune chronic hepatitis. A ctive prophylaxis of hepatitis A is possible. The elimination of hepat itis B is dependent on the recognition of viral determinants in associ ation with HLA proteins on infected hepatocytes by cytotoxic T cells. The specific epitopes recognized by B and T cells are being mapped. Po lymerase chain reaction (PCR) amplification and sequencing of genomic DNA in patients' with chronic hepatitis B has indicated that nucleotid e 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 prov e to be more effective immunomodulatory therapy. New nucleoside analog ues suppress HBV replication, but the safety of these drugs has been q uestioned after the appearance of severe liver toxicity with fialuridi ne. The data that hepatitis D virus is pathogenic has recently been ch allenged 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. Severa l isolates of hepatitis C virus have been cloned, and the sequence div ergence of these isolates indicates that there are several major genot ypes and component subtypes of this polymorphic virus. Hypervariabilit y of regions of the HCV envelope proteins may be important in persiste nce of HCV infection and immunopathogenesis. Type C hepatitis has a co mplex natural history, and several systemic manifestations as well as autoimmune disease have been linked to hepatitis C infection. Alpha in terferon is beneficial in 25-30% of patients; certain genotypes may be more sensitive to interferon therapy. The hepatitis E virus causes ac ute, and in susceptible populations, fulminant hepatitis. The diagnosi s can now be made with tests for anti-HEV and Polymerase chain reactio n. Other forms of viral hepatitis, particularly those associated with fulminant hepatitis, severe sporadic hepatitis and autoimmune disease are being sought.