Predictors of HBeAg Loss After Lamivudine Treatment for Chronic Hepatitis B

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JULY  2002 VIRAL HEPATITIS B-Predictors of HBeAg Loss After Lamivudine Treatment for Chronic Hepatitis B

R. P. Perrillo (1), C.L. Lai (2) ,Y.F. Liaw (3) , J. L. Dienstag (4), E. R. Schiff (5) ,S. W. Schalm (6) ,E. J. Heathcote(7) ,N. A. Brown (8) ,M. Atkins (9) , M.Woessner (10) , S.D. Gardner (10)

(1) Section of Gastroenterology and Hepatology, Ochsner Clinic Foundation, New Orleans,
(2) Department of Medicine, Queen Mary Hospital, Hong Kong, China;
(3) Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan;
(4) Gastrointestinal Unit (Medical Services) and Liver-Biliary-Pancreas Center, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA;
(5) Center for Liver Diseases, University of Miami Medical Center and the Veteran Affairs Medical Center, Miami, (6) Department of Hepatology and Gastroenterology, Erasmus University Hospital Rotterdam, Rotterdam, Netherlands;
(7) Division of Gastroenterology, Toronto Western Hospital, Toronto, Canada;
(8) Novirio Pharmaceuticals Inc., Cambridge, MA;
(9) Glaxo Wellcome Research and Development, Greenford, Middlesex, England;
(10) Glaxo Wellcome Inc., Research Triangle Park, NC.

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. (Hepatology;36,186-194, 2002)


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