Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial

Background, aim, and methods-Alpha interferon is the generally approved the rapy for HBe antigen positive patients with chronic hepatitis B, but its ef ficacy is limited. Lamivudine is a new oral nucleoside analogue which poten tly inhibits hepatitis B virus (HBV) DNA replication. To investigate the po ssibility of an additive effect of interferon-lamivudine combination therap y compared with interferon or lamivudine monotherapy, we conducted a random ised controlled trial in 230 predominantly Caucasian patients with hepatiti s B e antigen (HBeAg) and HBV DNA positive chronic hepatitis IZ. Previously untreated patients were randomised to receive: combination therapy of lami vudine 100 mg daily with alpha interferon 10 million units three times week ly for 16 weeks after pretreatment with lamivudine for eight weeks (n=75); alpha interferon 10 million units three times weekly for 16 weeks (n=69); o r lamivudine 100 mg daily for 52 weeks (n=82). The primary efficacy end poi nt was the HBeAg seroconversion rate at week 52 (loss of HBeAg, development of antibodies to HBeAg and undetectable HBV DNA). Results-The HBeAg seroconversion rate at week 52 was 29% for the combinatio n therapy, 19% for interferon monotherapy, and 18% for lamivudine monothera py (p=0.12 and p=0.10, respectively, for comparison of the combination ther apy with interferon or lamivudine monotherapy). The HBeAg seroconversion ra tes at week 52 for the combination therapy and lamivudine monotherapy were significantly different in the per protocol analysis (36% (20/56) v 19% (13 /70), respectively; p=0.02). The effect of combining lamivudine and interfe ron appeared to be mast useful in patients with moderately elevated alanine aminotransferase levels at baseline. Adverse events with the combination t herapy were similar to interferon monotherapy; patients receiving lamivudin e monotherapy had significantly fewer adverse events. Conclusions-HBeAg seroconversion rates at one year were similar for lamivud ine monotherapy (52 weeks) and standard alpha interferon therapy (16 weeks) . The combination of lamivudine and interferon appeared to increase the HBe Ag seroconversion rate, particularly in patients with moderately elevated b aseline aminotransferase levels, The potential benefit of combining lamivud ine and interferon should be investigated further in studies with different regimens of combination therapy.