Efficacy of lamivudine in patients with hepatitis B virus precore mutant infection before and after liver transplantation

OBJECTIVE: Hepatitis B virus (HBV) precore mutant infection is associated w ith a more severe liver disease and a poorer response to interferon. We eva luated the efficacy and tolerance of lamivudine to induce complete and sust ained suppression of viral replication in seven patients infected with HBV precore mutant (HBeAg-/HBeAb+/HBV DNA+) (in three patients mutation at codo n 1896 was detected by direct sequencing). METHODS: Of the seven patients, five had decompensated HBV cirrhosis in a r eplicative phase and were liver transplant candidates (Group A) and two pat ients underwent orthotopic liver transplantation (OLT) for HBV liver cirrho sis and developed recurrent HBV infection in the grafted liver (Group B). L amivudine 100 mg daily was administered orally for a period of 6-75 wk. RESULTS: After 6-8 wk lamivudine therapy was well tolerated and successfull y suppressed HBV replication to an undetectable serum level of HBV DNA by p olymerase chain reaction in six patients. In Group A, two patients underwen t successful OLT with no evidence of HBV reinfection 2-14 months later. Lam ivudine was continued after OLT with no episodes of rejection. Three patien ts died before a suitable liver could be found tone remained serum HBV DNA after 6 wk of lamivudine therapy). In Group B, 9-14 months after lamivudin e therapy both patients developed lamivudine resistance (increased liver en zymes, reappearance of serum HBsAg and HBV DNA [by hybridization]). In both patients liver histology had progressed and in both, mutation at codon 552 of the HBV polymerase gene was detected. CONCLUSIONS: Lamivudine is well tolerated in patients with decompensated li ver cirrhosis due to HBV precore mutant infection who are liver transplant candidates. In four patients (80%) potent suppression of viral replication was detected, allowing OLT to be performed. However, post-OLT, a resistant mutant developed under lamivudine therapy. Combination therapy with other a ntiviral agents should be evaluated to discourage the emergence of lamivudi ne-resistant mutants. (Am J Gastroenterol 1999;94:663-667. (C) 1999 by Am. Cell. of Gastroenterology).