Interferon alfa for chronic hepatitis B infection: Increased efficacy of prolonged treatment

Interferon alfa (IFN-alpha) is the primary treatment for chronic hepatitis B, The standard duration of IFN-alpha therapy is considered 16 weeks; howev er, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-alpha treatment in patients wit h chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen (HBeAg) seroconversion, we conduc ted a prospective, controlled, multicenter trial in which all patients were treated with a standard regimen of 10 million units IFN-alpha 3 times per week over 16 weeks. Patients who were still HBeAg-positive after 16 weeks o f therapy were randomized to prolongation of the identical regimen up to 32 weeks (prolonged therapy) or discontinuation of treatment (standard therap y). Among the 162 patients who entered the study, 27 (17%) were HBeAg-negat ive after the first 16 weeks of treatment, and 118 were randomized to stand ard or prolonged therapy. After randomization, a response (HBeAg seroconver sion and sustained hepatitis B virus [HBV]-DNA negativity) was observed in 7 of the 57 (12%) patients assigned to standard therapy versus 17 of the 61 (28%) patients assigned to prolonged therapy (P = .04), A low level of vir al replication after 16 weeks of treatment, as indicated by serum HBV-DNA v alues under 10 pg/mL, was found to be the only independent predictor of res ponse (52% vs. 0%; P < .001) during prolonged therapy. The prolonged IFN-al pha schedule was well tolerated in the large majority of patients. In chron ic hepatitis B, prolongation of IFN-alpha therapy up to 32 weeks is superio r to a standard course of 16 weeks. Those patients who exhibit a low level of viral replication at the end of the standard regimen benefit most from p rolonged treatment.