Hepatitis B: Treatment Strategies for Currently Available Drugs

Introduction: Renewal of Interest in the Treatment of Chronic Hepatitis B Antiviral therapy studies of hepatitis B were first published in the mid 1970s, nearly a decade before the first treatment trials were reported for hepatitis C. Yet much of the emphasis on antiviral therapy in the United States until very recently has been focused on the treatment of hepatitis C. This is due to a number of circumstances: 1) the excitement and clinical developments that followed the more recent discovery of the hepatitis C agent; 2) the extremely high frequency with which patients with hepatitis C become chronically infected (80% vs 5% for hepatitis B); 3) the far greater number of individuals (roughly 3 million vs 1.2 million for hepatitis B) who are chronically infected with the virus in the United States; and 4) an intense public and industry focus on the treatment of hepatitis C. In the past 5 years, however, interest and excitement in the field of hepatitis B therapeutics has undergone a resurrection owing to the development of nucleoside analogue inhibitors of hepatitis B virus (HBV) replication. The newer drugs are not only better tolerated than interferon, they are also considerably less expensive. Somewhat ironically, recent studies have suggested that pegylated interferon may be more effective than traditional interferon for hepatitis B, and this has led to renewed interest in interferon therapy for this disorder. Emerging data suggest that a combination of interferon and nucleoside analogue therapy may be even more effective than either agent alone. It is possible that this approach will even exceed the therapeutic benefit provided by pegylated interferon used in combination with the nucleoside analogue ribavirin for patients with hepatitis C. The majority of patients with chronic hepatitis B in the United States and Western Europe express hepatitis B early antigen (HBeAg) in blood. The current review is focused on the treatment of this type of patient. In contrast, more than 80% of cases in the Mediterranean region and as many as 30% to 40% of cases in Asia are of the HBeAg-negative variety. Although the same agents are used for HBeAgnegative chronic hepatitis B, responses tend not to be as sustained, and longer duration therapy is usually necessary.