The natural course of chronic hepatitis B virus infection and its management.

Chronic infection with the hepatitis B virus (HBV) runs a long natural course during which underlying changes in liver histology can progress to cirrhosis and hepatic decompensation, as well as to hepatocellular carcinoma. Therapeutic intervention is currently aiming at suppression of HBV replication by applying a number of pharmacological agents. For an optimum use of available therapies, good knowledge of the natural course of chronic infection, as well as of the role played by several viral, host, and environmental factors, is mandatory. The larger part of this chapter deals with how to treat the various subsets of patients with chronic hepatitis B (CHB), using mainly three first-line drugs: pegylated interferon-α2a, entecavir, and tenofovir, administered either in finite courses or indefinitely. The frequency of virological, serological, biochemical, and histological responses in the various subsets of patients, both during and after stopping treatment, is reviewed. It is stressed that the application of the highly potent antivirals entecavir and tenofovir, with acceptable safety records and with a high barrier to HBV resistance, represents major progress in the treatment of CHB. Despite the hitherto important developments in the treatment of viral hepatitis B, clinical cure of chronic HBV infection with HBsAg loss is achievable only in a few treated patients while eradication of HBV infection appears unrealistic. Development of new pharmacological agents acting at multiple targets of the replicative cycle of HBV may achieve higher efficacy and even cure of CHB.