Viral hepatitis

Hepatitis A is still the most frequently reported Vaccine preventable disea se. A reduction in the incidence will only be achieved by routine childhood vaccination rather than by targeted vaccination of high-risk groups. A lar ger vaccine program is warranted. Hepatitis B remains a large public health problem. Vaccination targeted to high-risk adults failed to decrease the incidence of hepatitis B virus (HBV ) infection. Sexual as well as nosocomial transmission remain serious probl ems. Vaccine escape variants have also been identified in newborns from inf ected mothers who had been vaccinated at birth. Clearance of HBV infection results from complex immune mechanisms including TH1 cytokines significantl y associated with HLA class Il alleles. Escape HBV mutants, especially prec ore mutants, influence the outcome. The sequences of the promoter and other critical regions were associated with severe activity. Lamivudine is a maj or advance in therapy of chronic hepatitis B which was recently approved in many countries. Although drug resistant mutants may be selected during the rapy, additional nucleoside analogues including adefovir are promising. Opt imal combination strategies of different active compounds need to be resear ched. Three per cent of the world population has been infected with hepatitis C v irus (HCV). Epidemiology has shifted from transfusion to non-transfusion se ttings. Intravenous drug abuse is currently the main risk but nosocomial in fection is also of concern. Three independent factors seem associated with fibrosis progression: age, daily alcohol consumption of 50 g or more and ma le gender. Median duration of progression to cirrhosis is about 30 years. A t the cirrhotic stage, about 3-5% of patients per year develop hepatocellul ar carcinoma. There is little evidence that direct cytopathicity plays a si gnificant role in liver cell injury. HCV also infects extrahepatic cells wh ich seems critical in the pathogenesis of the many extrahepatic manifestati ons. The recent identification of CD81 protein as one of the HCV receptor c andidates may help us to understand how chronic HCV infection may trigger a wide spectrum of clinical manifestations, autoimmune or even lymphoprolife rative, through potent continuous B cell activation in the context of Vario us host and/or environmental cofactors. Direct measurement of HCV RNA has c larified HCV replication kinetics and variability. Among patients with chro nic hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy pr oduced a response rate of 28% among those with genotype 1 and 66% with othe r genotypes. Similar differences were found for combination therapy among p atients who had relapsed following previous interferon (IFN) therapy. Viral load prior to treatment has been clearly shown to be predictive of respons e to interferon treatment, with increased viral load associated with decrea se rates of response. In patients nonresponsive to interferon, a second cou rse of interferon alone has no beneficial effect whereas combination therap y may induce response in 25%. In conclusion, combination therapy should be given in all situations. Viral eradication should not be the only objective of the treatment since histological improvement may be obtained despite pe rsisting Viral replication with prolonged maintenance of antiviral therapy. Curr Opin Infect Dis 12:481-490. (C) 1999 Lippincott Williams & Wilkins.