Lamivudine has been shown to improve liver function and reduce the need for liver transplantation (LT) in patients with decompensated HBeAg-positive cirrhosis. Nevertheless, there is only limited experience with lamivudine in patients with anti-HBe-positive/HBeAg-negative cirrhosis. The primary aim of this study was to determine whether lamivudine treatment improves liver function and subsequently pre-LT survival or delays or obviates the need for LT in patients with anti-HBe-positive/HBeAg-negative cirrhosis. Between July 1998 and June 2003, 20 consecutive patients awaiting LT were enrolled in the study. All patients showed active viral replication and were treated with lamivudine 100 mg daily. Significant clinical improvement, defined as a decrease in the Child-Pugh-Turcotte score by >or=2 points, was observed in 11 (55%) patients. The median change in the Child-Pugh-Turcotte score was -2 (range -5 to +2). The median time required to achieve a 2-point or greater reduction in Child-Pugh-Turcotte score was 6 months (range 3-12 months). In nine patients (45%), the Child-Pugh-Turcotte score decreased to <or=6 (Child's class A cirrhosis). At last follow-up, 14 (70%) patients were alive and waiting for LT, with a median LT-free survival of 36 months (range 12-63 months). One patient (5%) developed resistance to lamivudine with reappearance of HBV DNA after 48 months of treatment. In conclusion, our results provide further evidence to the notion that lamivudine is beneficial in patients with decompensated anti-HBe-positive/HBeAg-negative cirrhosis caused by actively replicating chronic hepatitis B.