Sequential therapy with adefovir dipivoxil and pegylated Interferon Alfa-2a
for HBeAg-negative patients
R. Moucari1,2,3, N. Boyer1,2,3, M.-P. Ripault1,2,3, C. Castelnau1,2,3, V.
Mackiewicz4, A. Dauvergne5, D. Valla1,2,3, M. Vidaud5, M.-H. N. Chanoine4,
P. Marcellin1,2,3
Financial Support: None Potential 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.
Journal of Viral Hepatitis
Volume 18, Issue 8, pages 580–586, August 2011
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.作者: StephenW 时间: 2011-7-20 12:15