Combination therapy of active HBsAg vaccination and interferon-alpha in interferon-alpha nonresponders with chronic hepatitis B

Treatment with interferon-alpha leads to cessation of viral replication in 30-40% of patients with chronic hepatitis B. Preliminary data suggest that therapeutic vaccination in patients with chronic HBV infection may be benef icial. The present trial was conducted to assess the efficacy of combinatio n therapy of interferon-alpha with HBsAg vaccination in patients who previo usly failed to respond to interferon-alpha alone. Eighteen patients positiv e for HBsAg and HBeAg were included. Mean ALT was 81 +/- 23 units/liter and 7 (39%) patients had HBV-DNA levels >2000 pg/ml. Patients received 5 milli on IU interferon-alpha 2b (Intron A) thrice weekly for six months and recom binant HBsAg (Gen H-B-Vax) at the beginning and 4 and 12 weeks after initia tion of interferon therapy. No serious side effects were seen during the tr ial period. Loss of HBeAg was seen in 39% (7/18), HBV DNA was undetectable in 50% (9/18), and ALT was normal in 56% 10/18) of patients six months afte r completion of therapy. Simultaneous administration of interferon-alpha an d HBsAg vaccination in patients previously not responding to interferon alo ne appears to be safe, well-tolerated, and it achieved response rates simil ar to or even higher than interferon in treatment naive patients. This comb ination therapy seems to offer a new and promising approach for patients wi th chronic hepatitis B virus infection.