Clinical Course of Lamivudine Monotherapy in Patients
Objectives: We have evaluated the efficacy of long-term lamivudine monotherapy in patients with decompensated HBeAg-negative/HBV-DNA positive cirrhosis.
Methods: We analyzed the clinical course and outcome of lamivudine treatment in 30 consecutive cirrhotics and compared with 30 HBV untreated historical HBeAg-negative controls matched for age and gender.
Results: Significant clinical improvement, defined as a reduction of at least two points in Child-Pugh score was observed in 23 of the 30 treated patients (76.6%) versus none of the 30 patients in the control group (p < 0.0001) after a mean follow-up of 20.6 ± 12.1(±SD) months. There were 10 deaths in the treated group versus 24 in the control group (p = 0.07). Liver-related deaths occurred in five of the eight patients soon after the development of biochemical breakthrough. Patients with clinical improvement had better survival than patients with no improvement (p = 0.04) or those who developed biochemical breakthrough due to YMDD mutants (p = 0.001).
Conclusions: Lamivudine significantly improves liver function in HBeAg-negative decompensated cirrhosis. However, the development of the biochemical breakthrough due to YMDD mutants is associated with fatal outcome.

Patients with decompensated cirrhosis due to chronic hepatitis B virus (HBV) infection have a poor prognosis. For the time being liver transplantation appears to be the only therapeutic option for these patients. However, the increasing number of liver transplant candidates, the long waiting lists, and the inadequate number of transplantation centers provide a treatment that can improve liver function, prolong survival, and delay transplantation necessary.

Lamivudine, a potent nucleoside analogue, is currently approved for the treatment of patients with chronic hepatitis B (CHB). Lamivudine is highly effective in a broad range of patients and has an excellent safety profile. Current evidence suggests that a 12-month course of lamivudine achieves normal transaminase levels and no detectable HBV DNA by a hybridization assay in 65% of patients with compensated HBeAg-negative/HBV DNA-positive liver disease. In decompensated liver disease lamivudine is associated with improvement of liver function. However, the high rates of biochemical and virological relapses soon after discontinuation of treatment and the emergence of drug-resistant hepatitis B mutants are the two major problems with lamivudine treatment. In HBeAg-positive CHB seroconversion may develop despite the emergence of the viral mutants, while in HBeAg-negative CHB the development of viral resistance seems to reduce the response rate. In decompensated HBeAg-negative cirrhotics the role of prolonged lamivudine monotherapy and the significance of the breakthrough phenomenon is still under investigation.

The primary aim of this study was to evaluate in patients with decompensated HBeAg-negative cirrhosis the efficacy and safety of prolonged lamivudine treatment. The secondary aim was to assess the outcome of patients who developed breakthrough infection during lamivudine treatment.