Sequential therapy with adefovir dipivoxil and pegylated Interferon Alfa-2a for HBeAg-negative patients


  • Financial Support: NonePotential

  • Conflict of Interest: P. Marcellin advises, is a consultant for, and is on the speakers’ bureau of Roche, Schering-Plough, Gilead, Bristol-Myers Squibb, GlaxoSmithKline, and Idenix-Novartis. He is a consultant for and advises Vertex, Valeant, Human Genome Sciences, Cythesis, Intermune, Wyeth, and Tibotec.

Rami Moucari, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy, France. E-mail:,


Summary.  To assess the impact of sequential therapy with adefovir dipivoxil (ADV) and pegylated interferon alfa-2a (PEG-IFN) on virological (serum HBV-DNA) and serological (serum HBsAg) response in 20 consecutive HBeAg-negative patients. Patients received ADV for 20 weeks, then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks. Serum HBV-DNA and HBsAg were assessed at baseline, during therapy (weeks 20, 44 and 68) and follow-up (weeks 92 and 116). Sustained virological response (SVR) was defined as serum HBV-DNA <10 000 copies/mL (partial) or <70 copies/mL (complete) 24 weeks after stopping treatment. A serological response was defined as a serum HBsAg decrease ≥1 log10IU/mL at the end of treatment. Baseline median serum HBV-DNA and HBsAg levels were 7.6 log10copies/mL and 3.8 log10IU/mL, respectively. Ten patients (50%) achieved SVR, six of them had partial response and four complete response. Four patients (20%) achieved serological response. Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0 log10IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at weeks 20, 44 and 68, respectively). On-treatment serum HBsAg decrease had a high accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients. Serum HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials are needed to explore this strategy with more potent analogues.