Predictors of HBeAg loss after lamivudine treatment for... : Hepatology (original) (raw)

Original Articles: PDF Only

Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B

Perrillo, Robert P.*,1; Lai, Ching-Lung2; Liaw, Yun-Fan3; Dienstag, Jules L.4; Schiff, Eugene R.5; Schalm, Solko W.6; Heathcote, Jenny E.7; Brown, Nathaniel A.8; Atkins, Mark9; Woessner, Mary10; Gardner, Stephen D.10

1Section of Gastroenterology and Hepatology, Ochsner Clinic Foundation, New Orleans, LA

2Department of Medicine, Queen Mary Hospital, Hong Kong, China

3Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan

4Gastrointestinal Unit (Medical Services) and Liver-Biliary-Pancreas Center, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA

5Center for Liver Diseases, University of Miami Medical Center and the Veteran Affairs Medical Center, Miami, FL

6Department of Hepatology and Gastroenterology, Erasmus University Hospital Rotterdam, Rotterdam, the Netherlands

7Division of Gastroenterology, Toronto Western Hospital, Toronto, Canada

8Novirio Pharmaceuticals Inc., Cambridge, MA

9Glaxo Wellcome Research and Development, Greenford, Middlesex, England

10Glaxo Wellcome Inc., Research Triangle Park, NC

E-mail:[email protected]

*Address reprint requests to: Section of Gastroenterology and Hepatology, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121. fax: 504-842-7466.

Received December 12, 2001; Accepted April 21, 2002; previously published online December 30, 2003

Abstract

Elevated alanine transaminase (ALT) levels and low serum hepatitis B virus (HBV) DNA predict a higher likelihood of hepatitis B e antigen (HBeAg) loss in patients with chronic hepatitis B treated with interferon. Predictors of HBeAg loss in patients treated with lamivudine are not known. The objective of this analysis of 4 lamivudine-controlled Phase III trials was to determine patient-dependent or laboratory variables that predict HBeAg loss. Predictors of HBeAg loss in patients treated with interferon, lamivudine plus interferon, or placebo are also described. A total of 805 adults with chronic hepatitis B were treated either with lamivudine (n = 406), matching placebo (n = 196), interferon (n = 68), or the combination of lamivudine plus interferon (n = 135). Demographic and baseline disease characteristics were used in stepwise multivariate analyses to identify features that were predictive of lamivudine-induced HBeAg loss. HBeAg loss correlated with increased pretreatment ALT levels in all groups. The rate of HBeAg loss was highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal (ULN) and was most pronounced in the lamivudine group (56%). Multivariate modeling indicated that elevated baseline ALT levels (P < .001) and histologic activity index (HAI) score (P < .001) were important predictors of HBeAg loss in response to lamivudine. The effect of pretreatment ALT levels on HBeAg loss was similar for Asians and Caucasians. In conclusion, elevated pretreatment ALT levels and/or active histologic disease were the most important predictors of lamivudine-induced HBeAg loss. Asians and Caucasians had similar rates of response to lamivudine at comparable ALT levels.