Hepatitis B infection: pathogenesis and management

Although hepatitis B is an ancient disease, most of the advances in our knowledge of its epidemiology, prevention, pathogenesis, natural history and treatment 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 significantly more time to overcome the social and economic hurdles. While there 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 new cases of HBV infection for many more years. Thus, HBV infection cannot be considered to be a health problem of the past. The focus of hepatitis B research at the turn of the millenium will be the development of more effective therapies that can be applied to all patients with chronic HBV infection. These treatments need to be effective in inhibiting HBV DNA synthesis and in eliminating ccc DNA. They may involve monotherapy with more potent antiviral 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 of 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 be addressed are the prevalence of occult HBV infection, the changing epidemiology and clinical significance of HBV variants, in particular the A1896 mutant, and the mechanisms of immune clearance and pathogenesis.