A three-month course of lamivudine therapy in HBeAg-positive hepatitis B patients with normal aminotransferase levels.

Background/aims: HBeAg-positive patients with normal ALT levels are unlikely to respond to current therapy. In addition, there is a high risk of hepatocellular carcinoma in HBeAg-positive patients in the natural course of HBV infection. For this purpose, we aimed to investigate the clinical efficacy and safety of a three-month course of lamivudine therapy in HBeAg-positive hepatitis B patients with normal aminotransferase levels for assessing a more practical and economical approach to these patients.

Methods: Forty-six patients were prospectively randomized into two groups. Group A consisted of 13 patients treated with lamivudine 100 mg/day, for 12 weeks [7 males, mean age 23.30+/-5.82 years, median ALT of 27 IU/L (21-40), median HBV DNA of 4116 pg/ml (2885-6628)]. Group B consisted of 33 patients without treatment [18 males, mean age 24.75+/-6.92 years, median ALT of 30 IU/L (19-39), median HBV DNA of 4094 pg/ml (782-7387)]. Main outcome measure was sustained virologic response, which was defined as loss of HBV DNA in serum with HBeAg seroconversion at least 12 months thereafter. Follow-up lasted 12 months after the first dose.

Results: No significant effects were observed in the treated population in the reduction of HBV DNA to undetectable levels, in HBeAg/anti-HBe seroconversion, or in transaminase levels. At the end of follow-up, sustained virologic response was almost similar in the study as well as control group (7.6% vs. 3.0%, p=0.502). None of the 13 patients who received lamivudine therapy had HBeAg seroconversion during the study period. In addition, the suppression of serum HBV DNA was temporary; prolonged suppression could be achieved in only one patient in the follow-up period. The median levels of HBV DNA and ALT values between baseline and month 12 did not differ significantly between groups. All patients remained HBsAg positive and none developed anti-HBs. The therapy was well tolerated and post-therapy flare was not observed in any patient after stopping lamivudine therapy.

Conclusions: A short course of lamivudine therapy resulted mostly in only temporarily depressed serum HBV DNA levels without significant change in viral clearance. Whether permanent suppression of HBV DNA can be achieved in this special population of HBsAg carriers by long-term treatment with lamivudine awaits further controlled trials. New and safe modalities of therapy are needed for the satisfactory treatment of these asymptomatic but viremic patients.