HBeAg and hepatitis B virus DNA as outcome predictors... : Hepatology (original) (raw)

Viral Hepatitis

HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B

Fried, Michael W.1*; Piratvisuth, Teerha2; Lau, George K. K.3; Marcellin, Patrick4; Chow, Wan-Cheng5; Cooksley, Graham6; Luo, Kang-Xian7; Paik, Seung Woon8; Liaw, Yun-Fan9; Button, Peter10; Popescu, Matei11

1 University of North Carolina, Chapel Hill, NC

2 NKC Institute of Gastroenterology and Hepatology, Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand

3 Department of Medicine, Queen Mary Hospital, University of Hong Kong, China

4 Service d'Hépatologie, Institut National de la Santé et de la Recherche Médicale Unité 481 and Centre de Recherches Claud Bernard sur les Hépatite Virales, Hôpital Beaujon, University of Paris, Clichy, France

5 Gastroenterology Department, Singapore General Hospital, Singapore

6 Clinical Research Department, Royal Brisbane Hospital, Brisbane, Australia

7 Department of Infectious Diseases, Nangfang Hospital, Guangzhou, China

8 Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

9 Liver Research Unit, Chang Gung Memorial Hospital, Linkou, Taiwan

10 Roche, Dee Why, Australia

11 Roche, Basel, Switzerland

*Address reprint requests to: University of North Carolina Liver Program, CB 7584, 8015 Burnett-Womack Building, University of North Carolina, Chapel Hill, NC 27599-7584

Email:[email protected]

Received 28 February 2007; Accepted 26 September 2007

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

Grant sponsor: Roche, Basel, Switzerland; Grant sponsor: Unknown funding agency; Grant Numbers: K24 DK06614 RR000046.

Potential conflict of interest: Dr. Fried has received research grants for clinical research and honoraria for speaking at symposia. He has no stock ownership, equity interest, or patent-licensing arrangement with Roche. Dr. Fried is a consultant for Roche. Dr. Piratvisuth advises, is on the speakers' bureau of, and received grants from Roche, Novartis, Schering-Plough, and GlaxoSmithKline. He also received grants from Bristol-Myers Squibb. Drs. Paik and Cooksley received grants from Roche. Dr. Lau received grants from Roche, Gilead, and Novartis. Dr. Marcellin is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche, Schering-Plough, Gilead, Bristol-Myers Squibb, GlaxoSmithKline, Vertex, Idenix-Novartis, Valeant, Human Genome Sciences, Coley Pharma, Cytheris, Intermune, Wyeth, and Tibotec.

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Abstract

The aims of this study were to evaluate the usefulness of quantitative hepatitis B e antigen (HBeAg) values for predicting HBeAg seroconversion in patients treated with peginterferon alfa-2a and to assess the dynamic changes in quantitative HBeAg during therapy, compared with conventional measures of serum hepatitis B virus DNA. Data were analyzed from a large, randomized, multinational phase III registration trial involving 271 HBV-infected HBeAg-positive patients who received peginterferon alfa-2a plus oral placebo for 48 weeks. HBeAg levels were measured serially during therapy using a microparticle enzyme immunoassay validated with in-house reference standards obtained from the Paul Ehrlich Institute (PEIU/mL). In patients who achieved HBeAg seroconversion, levels of HBeAg consistently decreased during treatment and remained at their lowest level during the 24 weeks of posttreatment follow-up. After 24 weeks of treatment, 4% of patients with the highest levels of HBeAg (≥100 PEIU/mL) achieved HBeAg seroconversion, yielding a negative predictive value of 96%, which was greater than that obtained for levels of HBV DNA (86%). Late responders to peginterferon alfa-2a could also be differentiated from nonresponders by continued decrease in HBeAg values, which were not evident by changes in HBV DNA. Conclusion: These analyses suggest quantitative HBeAg is a useful adjunctive measurement for predicting HBeAg seroconversion in patients treated with peginterferon when considering both sensitivity and specificity compared with serum HBV DNA. (Hepatology 2008;47:428–434.)

Abbreviations: HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; NPV, negative predictive value.