Demonstration of mutations conferring resistance to lamivudine in liver tissue of chronic hepatitis B patients under lamivudine therapy

Abstract

Aim: To demonstrate the genotypic lamivudine resistance in liver tissue of patients with negative serum hepatitis B virus (HBV) DNA under long-term lamivudine therapy. Materials and methods: Fourteen patients (10 patients with elevated alanine aminotransferase and 4 patients under long-term lamivudine therapy for severe liver disease) with undetected serum HBV DNA were included in the study. A liver biopsy was performed for each patient, and HBV DNA extracted from liver tissue was analyzed with TaqMan real-time polymerase chain reaction. Results: Mutations conferring lamivudine resistance were shown for all 14 patients in their liver tissue-extracted HBV DNA. One patient had rtM204V, 4 patients had rtL180M, 2 had rtL180M + rtM204V, 4 had rtL180M + rtM204I, and 3 had rtL180M + rtM204I + rtM204V substitutions. Conclusion: Analyzing mutation in liver tissues of these patients might help demonstrate resistance earlier and prevent delaying of therapeutic modification. Therefore, all liver biopsy specimens of patients with severe liver fibrosis should be analyzed using the molecular technique. © TÜBİTAK.