Efficacy and safety of pegylated interferon-alpha 2a in patients with lamivudine-resistant HBeAg-positive chronic hepatitis B

Abstract

Background: Lamivudine resistance develops in up to 80% of patients with chronic hepatitis B (CHB) after 5 years of treatment. Cross-resistance between nucleoside/ nucleotide analogues limits management options in these patients. To investigate the role of pegylated interferon-alpha 2a as rescue therapy in these patients, the efficacy and safety of pegylated interferon-alpha 2a between treatment-naive patients and lamivudine-resistant patients with hepatitis B e antigen (HBeAg)-positive CHB were compared. Methods: A total of 150 HBeAg-positive CHB patients were stratified according to prior treatment. Lamivudine-resistant patients (n=64) and treatment-naive patients (n=86) received pegylated interferon-alpha 2a once-weekly for 48 weeks and were followed-up for an additional 24 weeks. Primary end points were HBeAg loss and HBV DNA < 100,000 copies/ml at end of follow-up. Results: A total of 65 (76%) treatment-naive patients and 49 (77%) lamivudine-resistant patients completed treatment and 24 weeks of follow-up. Rates of HBeAg loss were comparable at end of follow-up between treatment- naive patients and lamivudine-resistant patients (20.9% and 23.4%, respectively; P=0.8423). Similarly, rates of HBV DNA< 100,000 copies/ml were comparable at end of follow-up between treatment-naive patients and lamivudine-resistant patients (20.9% and 21.9%, respectively; P=1.000). There was no statistically significant difference in alanine aminotransferase normalization rates between treatment-naive patients and lamivudine-resistant patients (36.0% and 29.7%, respectively; P= 0.4848). A total of one patient in each group achieved hepatitis B surface antigen (HBsAg) loss and seroconversion. The most common adverse events were those known to occur with pegylated interferon-alpha 2a therapy, and safety profiles were similar between both patient populations. Conclusions: Pegylated interferon-alpha 2a may be effective as a rescue therapy in patients with lamivudine-resistant HBeAg-positive CHB.