Efficacy of lamivudine therapy for advanced liver disease in patients with precore mutant hepatitis B virus infection awaiting liver transplantation

Background. Orthotopic liver transplantation (OLT) for end-stage liver disease resulting from hepatitis B virus (HBV) infection is associated with a high rate of recurrence and reduced survival. Lamivudine is effective in inhibiting HBV replication in patients with chronic hepatitis. This study evaluated the impact of lamivudine on viral suppression, liver function, and disease severity in patients awaiting OLT with HBV e-minus strain infection. Methods. Twenty-five patients received lamivudine (100 mg per day) from the day of listing for OLT. All patients were positive for serum HBV-DNA by polymerase chain reaction and all had a Child-Pugh score of 7 or higher. Results. Patients were followed for 12+/-9 months (mean +/-SD). Eleven underwent OLT within 13 months of treatment initiation, one died after 10 months, and one dropped out after 3 months. After 3, 6, and 9 months, HBV-DNA by polymerase chain reaction was undetectable in 14 of 25, 14 of 20, and 13 of 15 patients, respectively. Two patients developed lamivudine resistance after 9 and 18 months of treatment, respectively, without liver decompensation. Comparing baseline to last visit data, a significant improvement in prothrombin activity (43+/-15% vs. 52+/-19%; P=0.0014), serum bilirubin (3.4+/-1.9 vs. 2.5+/-2.2 mg/dL; P=0.0007), serum albumin (3.3+/-0.3 vs. 3.6+/-0.5 g(dL; P=0.0278), presence of ascites (15/25 vs. 7/25; P=0.0047), and Child-Pugh score (9 vs. 8; P=0.0003) was observed. Because of liver function improvement, four patients were placed on low priority status for OLT (United Network of Organ Sharing 3) and 9 on inactive status (United Network of Organ Sharing 7). The overall probability of survival at 6 and 12 months was 100% and 90.9%, respectively. Conclusions. Lamivudine has an important role in patients with end-stage liver disease caused by HBV precore mutant strain. Not only does HBV-DNA suppression allow patients to be eligible for OLT, but the improvement of the patients' clinical status may delay the need for OLT in an era of organ shortage.