Hepatitis B infection: pathogenesis and management

Although hepatitis B is an ancient disease, most of the advances in our kno wledge of its epidemiology, prevention, pathogenesis, natural history and t reatment were made in the last 30 years. The prospect of global eradication of HBV infection within the next 50 years is technologically possible but implementation of worldwide vaccination against hepatitis B will require si gnificantly more time to overcome the social and economic hurdles. While th ere is reasonable optimism that HBV infection will be eradicated, there are currently 300 million HBV carriers worldwide who are at risk of dying from liver failure or hepatocellular carcinoma, and there will continue to be n ew cases of HBV infection for many more years. Thus, HBV infection cannot b e considered to be a health problem of the past. The focus of hepatitis B r esearch at the turn of the millenium will be the development of more effect ive therapies that can be applied to all patients with chronic HBV infectio n. These treatments need to be effective in inhibiting HBV DNA synthesis an d in eliminating ccc DNA. They may involve monotherapy with more potent ant iviral agents that do not induce resistance, but are more likely to require a combination of antiviral agents or antiviral and immunomodulatory agents . These treatments must be safe, convenient to administer, and affordable. It is likely that new therapies with increasing efficacy will be available in the next one to two decades and combination therapy will be used widely by 2010. These treatments will induce sustained remission in the majority o f patients who can afford them but provision of treatment to all those who need them will be more difficult. Other areas of hepatitis B that need to b e addressed are the prevalence of occult HBV infection, the changing epidem iology and clinical significance of HBV variants, in particular the A1896 m utant, and the mechanisms of immune clearance and pathogenesis.