Hepatitis B virus rebound common in patients receiving nucleoside analogs for chronic hepatitis B

A rebound of the Hepatitis B virus is common in patients receiving nucleoside analogs for chronic hepatitis B, according to a study from U-M hepatologists. But nearly 40% of the rebounds or virological breakthroughs (VBTs) were not related to antiviral drug resistance.

Details of this retrospective study will be published in the print May issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases. The paper is available online.

"This study underscores the need for patients to take their medicines regularly to derive optimal response," says lead author Anna S. Lok, M.D., professor of internal medicine in the University of Michigan Medical School's Division of Gastroenterology.

"These results emphasize that there is a danger of misdiagnosis of drug resistance and unnecessary modifications to treatment regimen when it could be patients not adhering to their drug regimen."

VBT is the first manifestation of antiviral drug resistance during nucleoside analog therapy of chronic hepatitis B. Nucleoside analog drugs approved for treatment of chronic hepatitis B include lamivudine, adefovir , entecavir, telbivudine and tenofovir (TDF). While the medications suppress the virus with few side effects, they do not eradicate hepatitis B and require long-term treatment to provide clinical benefit. With long-term nucleoside analog therapy, studies have shown an increasing risk of drug resistance particularly with monotherapy regimens.

In the current study, Lok and colleagues from the University of Michigan Health System examined the incidence of VBT and genotypic resistance in 148 patients with chronic hepatitis B who were treated with nucleoside analogs between January 2000 and July 2010. The mean age of study participants was 45 years and 73% were male.

Results showed that during a mean follow-up of 38 months, 39 (26 percent) of patients had at least one VBT, and upon retesting, 38 percent of these patients did not have a VBT and 10 (38 percent) had no evidence of genotypic resistance. Researchers reported the probability of VBT, confirmed VBT, and genotypic resistance at five years was 46%, 30%, and 34%, respectively.

"Our analysis showed an alarmingly high rate of VBT in clinical practice and the only factor significantly linked to VBT was failure to achieve undetectable hepatitis B virus DNA," says Lok.

HBV DNA decreased in the ten patients who initially experienced a VBT, but who did not have confirmed VBT or GR, when the same drug regimen was maintained. Nine of these patients had undetectable HBV DNA at the most recent follow-up, a mean of 7 months after the initial VBT. These data suggest that nonadherence to medication may be a common cause of VBT.

"Counseling patients with chronic hepatitis B on the importance of medication adherence, and confirming reemergence of the virus and genetic mutations that cause resistance, can help to avoid unnecessary changes to antiviral treatments," says Lok.

SOURCE University of Michigan Medical School