Efficacy and Safety of Peginterferon Alfa-2a in Patients with Lamivudine-resistant HBeAg-positive Chronic Hepatitis B 

Suh D, Lee H, Byun K, Cho M, Kweon Y, Tak W, Chon C, Koh K, Lee Y

BACKGROUND Lamivudine resistance develops in up to 80% of patients with chronic hepatitis B (CHB) after 5 years of treatment. Cross-resistance between nucleos(t)ide analogues limits management options in these patients. To investigate the role of peginterferon alfa-2a as rescue therapy in these patients, the efficacy and safety of peginterferon alfa-2a between treatment-naïve 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-naïve patients (n=86) received peginterferon alfa-2a once-weekly for 48 weeks and were followed-up for an additional 24 weeks. Primary endpoints were HBeAg loss and hepatitis B virus (HBV) DNA less than 100,000 copies/mL at end of follow-up.

RESULTS A total of 65 (76%) treatment-naïve 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-naïve patients and lamivudine-resistant patients (20.9% and 23.4%, respectively; p=0.8423). Similarly, rates of HBV DNA less than 100,000 copies/mL were comparable at end of follow-up between treatment-naïve 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-naïve patients and lamivudine-resistant patients (36.0% and 29.7%, respectively; p=0.4848). 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 peginterferon alfa-2a therapy and safety profiles were similar between both patient populations.

CONCLUSIONS Peginterferon alfa-2a may be effective as a rescue therapy in patients with lamivudine-resistant HBeAg-positive CHB.