Combination of Peginterferon Alfa-2b and Lamivudine Is Superior to Lamivudine Alone in the Treatment of Chronic Hepatitis B Infection

Treatment of chronic hepatitis B infection is still unsatisfactory and previous studies combining conventional interferon with lamivudine yielded conflicting results. The aim of this prospective, randomized study set was to evaluate the efficacy and safety of peginterferon alfa-2b (PEG-Intron) and lamivudine (Epivir-HBV) combination for chronic hepatitis B infection.

HBeAg-positive treatment-naive patients were randomized to receive either a combination of 32-week peginterferon alfa-2b (1.5mcg/kg/wk, max 100mcg) and 52-week lamivudine (100mg daily) or 52-week lamivudine (100mg) monotherapy alone.

HBV DNA levels (measured by TaqMan real-time PCR assay), HBeAg status, HBV genotype, drug resistant mutant (INNO-LiPA HBV DR line probe assay), serum transaminase levels were monitored. Pre- and post-treatment liver histology (necro-inflammatory score according to Knodell system and fibrosis score according to Ishak system) were compared.

The primary endpoint was sustained virological response (HBeAg seroconversion and HBV DNA <500,000 copies/ml) at 24 weeks after finishing medication.

Secondary endpoints include end-of-treatment virological response, reduction in HBV DNA levels, biochemical responses and histologic necro-inflammatory and fibrosis scores.

Results

100 patients were randomized into the 2 treatment groups. Sustained virological response was significantly higher in combination therapy than lamivudine monotherapy (p=0.03).

At the end of treatment, patients receiving combination therapy had a higher rate of virological response (60% vs 28%, p=0.003), had more substantial reduction of log10 HBV DNA (3.91 vs 2.83, p<0.001) and were less likely to have lamivudine resistant mutant (21% vs 40% p=0.045) than those who received lamivudine monotherapy.

The median reduction in necro-inflammatory score in the combination group and lamivudine monotherapy group were 2 and 3 respectively (p=0.21).

There was no significant change in the median fibrosis score in the two treatment groups.

The authors conclude, “In patients with HBeAg-positive chronic hepatitis B infection, combination of peginterferon alfa-2b and lamivudine yielded significantly better results than lamivudine monotherapy.”

05/21/04

Reference
J J Y Sung and others. Combination of PegInterferon Alfa-2b and Lamivudine is Superior to Lamivudine Alone in the Treatment of Chronic Hepatitis B Infection (Abstract 410—plenary). Digestive Disease Week 2004. May 15-20, 2004. New Orleans, LA.