Early serum HBsAg drop: A strong predictor of sustained... : Hepatology (original) (raw)

Viral Hepatitis

Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients#

Moucari, Rami1,2,3; Mackiewicz, Vincent4; Lada, Olivier1,2,3; Ripault, Marie-Pierre1,2,3; Castelnau, Corinne1,2,3; Martinot-Peignoux, Michelle1,2,3; Dauvergne, Agnes5; Asselah, Tarik1,2,3; Boyer, Nathalie1,2,3; Bedossa, Pierre6; Valla, Dominique1,2,3; Vidaud, Michel5; Nicolas-Chanoine, Marie-Hélène4; Marcellin, Patrick1,2,3*†

1 Service d'Hépatologie, Hôpital Beaujon, Clichy, France

4 Service de Microbiologie, Hôpital Beaujon, Clichy, France

5 Service de Biochimie, Hôpital Beaujon, Clichy, France

6 Service d'Anatomie-Pathologique, Hôpital Beaujon, Clichy, France

2 INSERM U773-CRB3, Paris, France

3 Université Denis Diderot-Paris 7, Paris, France

* Service d'Hépatologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy, France

Email:[email protected]

Received July 18, 2008; accepted November 11, 2008.

Published online 28 December 2008 in Wiley InterScience (www.interscience.wiley.com).

# Potential conflict of interest: Dr. 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. He also advises Coley Pharma.

† fax: (33)-1-47-30-94-40.

Abstract

Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) in 20% of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. In addition, loss of hepatitis B surface antigen (HBsAg) is achieved with a 10% yearly rate after treatment cessation in sustained responders. The aim of this study was to assess on-treatment serum HBsAg kinetics to predict SVR in HBeAg-negative patients treated with PEG-IFN. Forty-eight consecutive patients were treated with PEG-IFN (180 μg/week) for 48 weeks. Serum hepatitis B virus (HBV) DNA (COBAS TaqMan) and HBsAg (Abbott Architect HBsAg QT assay) were assessed at baseline, during treatment (weeks 12, 24, and 48), and during follow-up (weeks 72 and 96). SVR was defined as undetectable serum HBV DNA (<70 copies/mL) 24 weeks after treatment cessation. Twenty-five percent of patients achieved SVR. They were not different from those who failed treatment regarding age, sex, ethnicity, HBV genotype, baseline serum HBV DNA and HBsAg levels, or liver histology. During treatment, serum HBsAg levels decreased only in patients who developed SVR, with mean decreases of 0.8 ± 0.5, 1.5 ± 0.6, and 2.1 ± 1.2 log10 IU/mL at weeks 12, 24, and 48, respectively. A decrease of 0.5 and 1 log10 IU/mL in serum HBsAg levels at weeks 12 and 24 of therapy, respectively, had high predictive values of SVR (negative predictive value [NPV] 90%, positive predictive value [PPV] 89% for week 12; NPV 97%, PPV 92% for week 24). HBsAg loss was observed in three patients, all with SVR. Conclusion: Early serum HBsAg drop has high predictive values of SVR to PEG-IFN in HBeAg-negative CHB patients. Serum quantitative HBsAg may be a useful tool to optimize the management of PEG-IFN therapy in these patients. (Hepatology 2009.)