Peginterferon-α2a combined with response-guided short-term lamivudine improves response rate in hepatitis B e...

The hepatitis B e antigen (HBeAg) seroconversion rate in HBeAg-positive chronic hepatitis B patients treated with peginterferon-α2a (peg-IFN α2a) is still low (about 30%). The aim of this study was to find a new combination therapy of peg-IFN α2a with lamivudine to improve the efficacy in HBeAg-positive chronic hepatitis B patients.

All patients started with peg-IFN α2a treatment at a dose of 135 μg/week. If the concentration of hepatitis B virus (HBV) DNA was greater than 1.0×10 copies/ml and if the patient was positive for HBeAg at 12 weeks of treatment, lamivudine was included into the treatment for 12 weeks. Thereafter, the patients continued on peg-IFN α2a alone for the full 52-week treatment course.

Thirty-two patients were recruited, and eight of them achieved HBV DNA concentrations of less than 1.0×10 copies/ml or HBeAg loss at 12 weeks of treatment when lamivudine was not administered (group A). The other 24 patients received additional lamivudine, started from 12 weeks of treatment for 12 weeks (group B). At the end of treatment (EOT), in the peg-IFN α2a monotherapy group (group A), eight patients (100%) had HBV DNA loss, six patients (75%) achieved HBeAg seroconversion, and eight patients (100%) achieved alanine aminotransferase (ALT) normalization. This level of response was sustained for 24 weeks after treatment in all patients with an early response. In the peg-IFN α2a combined short-term lamivudine group (group B), 12 patients (50%) had HBV DNA loss, nine patients (38%) achieved HBeAg seroconversion, one patient (4%) achieved hepatitis B surface antigen loss, and 15 patients (63%) achieved ALT normalization at EOT. One patient had an HBV DNA rebound and an HBeAg reversion 24 weeks after treatment. The total HBV DNA loss rate, HBeAg seroconversion rate, hepatitis B surface antigen loss rate, and ALT normalization rate in all patients were 59, 47, 3, and 69%, respectively, at EOT and were 56, 44, 3, and 69% 24 weeks after treatment, respectively.

This study indicates that the response-guided approach resulted in an overall HBeAg seroconversion rate of 47% at EOT and 44% 24 weeks after treatment. This promising strategy to increase response rates with peg-IFN α2a warrants further investigation.