Background Better treatments for chronic hepatitis B are needed.Lamivudine, the (-)enantiomer of 3'-thiacytidine, is a potentinhibitor of hepatitis B virus (HBV).
Methods In a double-blind trial, we randomly assigned 32 patientswith chronic hepatitis B (including 17 who had no response toearlier treatment with interferon) to receive 25, 100, or 300mg of oral lamivudine daily for 12 weeks. The patients werethen followed for 24 additional weeks. All the patients hadhepatitis B e antigen in serum.
Results Levels of HBV DNA became undetectable (<1.5 pg permilliliter) in 70 percent of the patients who received the 25-mgdose of lamivudine and 100 percent of those treated with the100-mg or 300-mg dose. in most patients, HBV DNA reappearedafter therapy was completed; however, six patients (19 percent),including five who had not responded to interferon, had sustainedsuppression of HBV DNA accompanied by normalization of alanineaminotransferase levels. Hepatitis B e antigen disappeared infour of these six patients (12 percent), three of whom had hadno response to interferon. Levels of HBV DNA fell in all patients,including those who had had high levels at base line or normalalanine aminotransferase levels at base line, but sustainedresponses were more likely in patients with initially low HBVDNA levels and high alanine aminotransferase levels. Duringor after therapy, alanine aminotransferase levels at least doubledin five patients (50 percent) given the 25-mg dose and eightpatients (36 percent) given the 100-mg or 300-mg dose. Minoradverse events occurred that were not related to the dose, asdid transient, asymptomatic elevations of amylase, lipase, andcreatine kinase levels.
Conclusions In a preliminary trial, 12 weeks of lamivudine therapywas well tolerated, and daily doses of 100 mg and 300 mg reducedHBV DNA to undetectable levels.
Source Information
From the Gastrointestinal Unit and Liver–Biliary–Pancreas Center, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston (J.L.D.); the Division of Gastroenterology, Ochsner Clinic, New Orleans (R.P.P.); the Center for Liver Diseases, University of Miami School of Medicine and the Veterans Affairs Medical Center, Miami (E.R.S., M.B.); and Glaxo Research Institute, Research Triangle Park, N.C. (C.V., M.R.). Presented in part at the 45th Annual Meeting of the American Association for the Study of Liver Diseases, Chicago, November 14, 1994, and in abstract form (Hepatology 1994;20:199).
Address reprint requests to Dr. Dienstag at the Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114.
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