Effects of antiviral agents on chronic hepatitis B. Analysis using Cox proportional hazard model

Two hundred fifteen courses of antiviral treatment including interferon with or without steroid withdrawal, adenine arabinoside with steroid withdrawal, and steroid withdrawal alone were given to 175 patients with HBe-antigen positive chronic hepatitis B. The effectiveness was judged on loss of HBe antigen and formation of anti-HBe, and was compared with 80 controls. According to cumulative HBe seronegative and seroconversion rates as analyzed by the Kaplan-Meier method, interferon with steroid withdrawal increased both the cumulative HBe seronegative and seroconversion rates significantly (P < 0.0001). Adenine arabinoside with steroid withdrawal and interferon alone increased the cumulative HBe seronegative rate only (P < 0.001). The Cox proportional hazard regression model was fitted to the data of 188 cases whose pretreatment liver biopsy specimens were obtained. Among treatment protocols, interferon with steroid withdrawal shortened both the HBeAg-positive period and the duration until anti-HBe becomes reactive significantly (P < 0.0001). Interferon without steroid withdrawal and adenine arabinoside with steroid withdrawal shortened the HBeAg positive interval only (P < 0.05). Among patients' characteristics, female and advanced liver histology were favorable factors. Effects of treatment protocols were analyzed after averaging each parameter of the patients' characteristics. Interferon and adenine arabinoside with steroid withdrawal shortened the HBeAg-positive interval significantly (P < 0.0001 and P < 0.05, respectively), and interferon alone showed a tendency to shorten the interval. In particular, interferon with steroid withdrawal increased the chance of losing HBeAg 7.3 times more than control. The effectiveness of antiviral treatment on chronic hepatitis B, especially the priority of interferon with steroid withdrawal, was thought to be established through this study.