Emergence of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy / 대한내과학회지

ABSTRACT

BACKGROUND: The emergence of YIDD or YVDD mutant hepatitis B virus (HBV), with point mutation in the YMDD motif of DNA polymerase gene, has been reported in patients with lamivudine treatment group. The aims of this study was to investigate the emergence of mutant HBV during long-term lamivudine therapy using nested polymerase chain reaction (PCR) method and direct DNA sequencing. METHODS: Twenty-one chronic hepatitis B patients with HBeAg and HBV DNA positive were evaluated. During lamivudine therapy, there were reported breakthroughs of HBV DNA (over 50 pg/mL) when investigated the emergence of YMDD mutants by nested PCR method using restriction fragment length polymorphism (RFLP) in all patients. Direct DNA sequencing of HBV DNA polymerase gene including YMDD motif was also performed. RESULTS: There were 13 patients (61.9%) with YIDD mutant and 8 patients (38.1%) with YVDD mutant. The results of direct DNA sequencing were consistent with those of nested PCR data based on RFLP. The breakthrough was occurred at 15 to 106 weeks (57.9+/-23.6). At the point of breakthrough, the level of ALT was 74.8+/-117.7 (14-546) IU/L, and it was lower than the level of ALT before the therapy. CONCLUSION: In the long-term therapy of lamivudine, the emergence of YMDD motif mutant HBV was related to the breakthrough of HBV DNA and YIDD mutant was frequent. The nested PCR method using RFLP may be simple and sensitive to detect the YMDD motif mutant HBV.