Background. Better treatments for chronic hepatitis B are needed. Lamivudine, the (-)enantiomer of 3'-thiacytidine, is a potent inhibitor of hepatitis B virus (HBV). Methods. In a double-blind trial, we randomly assigned 32 patients with chronic hepatitis B (including 17 who had no response to earlier treatment with interferon) to receive 25, 100, or 300 mg of oral lamivudine daily for 12 weeks. The patients were then followed for 24 additional weeks. All the patients had hepatitis B e antigen in serum. Results. Levels of HBV DNA became undetectable (≤1.5 pg per milliliter) in 70 percent of the patients who received the 25-mg dose of lamivudine and 100 percent of those treated with the 100-mg or 300-mg dose. In most patients, HBV DNA reappeared after therapy was completed; however, six patients (19 percent), including five who had not responded to interferon, had sustained suppression of HBV DNA accompanied by normalization of alanine aminotransferase levels. Hepatitis B e antigen disappeared in four of these six patients (12 percent), three of whom had had no response to interferon. Levels of HBV DNA fell in all patients, including those who had had high levels at base line or normal alanine aminotransferase levels at base line, but sustained responses were more likely in patients with initially low HBV DNA levels and high alanine aminotransferase levels. During or after therapy, alanine aminotransferase levels at least doubled in five patients (50 percent) given the 25-mg dose and eight patients (36 percent) given the 100- mg or 300-mg dose. Minor adverse events occurred that were not related to the dose, as did transient, asymptomatic elevations of amylase, lipase, and creatine kinase levels. Conclusions. In a preliminary trial, 12 weeks of lamivudine therapy was well tolerated, and daily doses of 100 mg and 300 mg reduced HBV DNA to undetectable levels.
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