Trials test combination treatment for chronic hepatitis B in adults and children

Two clinical trials of a combination drug therapy—one in adults and another in children—found it was of limited benefit in treating chronic hepatitis B. Hepatitis B is a major health problem around the world and in the United States, particularly in people of Asian or African origin who emigrate from countries without the long-term universal vaccination and screening programs in this country. The chronic form of the disease can progress to cirrhosis and liver cancer, if not successfully treated. Infection with the hepatitis B virus (HBV) often occurs at birth or in childhood. Unlike hepatitis C, no relatively short course of a drug or combination of drugs has been found to elicit a long-term response in people with chronic hepatitis B, for which the most effective drugs available need to be taken for years, decades, or even life-long.

The NIDDK’s Hepatitis B Research Network is a multi-center study of both children and adults with hepatitis B at 28 sites throughout the United States and Canada, with a goal to better understand the natural history of hepatitis B and disease processes, and to test therapy approaches. The aim of these two Network trials, in adults and children, was to determine the safety and benefit of therapy with a limited course of a combination of drugs in the early phase of chronic HBV infection. In this phase, infected persons have no symptoms or abnormal liver tests, despite high levels of HBV in the bloodstream (called “immune tolerant” chronic hepatitis B). In both the adult and pediatric trials, 90 percent or more of participants were of Asian ancestry. The adult cohort had equal numbers of men and women, while 75 percent of the pediatric participants were girls. The treatment regimen was entecavir—a once-a-day, oral direct-acting antiviral drug—to which was added peginterferon, an immune- stimulating protein given weekly by injection. Entecavir was given alone for 8 weeks and then combined with peginterferon for the following 40 weeks. Researchers conducting the trials measured success by how well the combination therapy decreased levels of HBV DNA and proteins (called “HBeAg” and “HBsAg”) in the blood, and whether the 48 weeks of treatment led to a permanent loss of the viral proteins and DNA, as measured 48 weeks after stopping treatment. With treatment, levels of HBeAg, HBsAg, and HBV DNA decreased in all patients. However, none of the 27 adult trial participants and only three of the 60 children (5 percent) experienced complete resolution of hepatitis B, losing both viral proteins and DNA and developing antibodies during the 48 weeks following treatment.

Thus, this particular combination treatment was found to be of limited benefit in adults and children at the early, mild stage of chronic hepatitis B infection. Yet, this study offers promising evidence that a complete response to therapy could be achievable in people with chronic hepatitis B. In particular, the dramatic and complete response seen in a small proportion of children suggests that combination therapy—using these drugs, together with another agent(s)—is likely to achieve a beneficial response in a high proportion of people with chronic hepatitis B.