Predominance of hepatitis B virus YMDD mutants is prognostic of viral DNA breakthrough

Gastroenterology
Chang Hong LeeSun Pyo Hong

Abstract

Hepatitis B virus (HBV) tyrosine, methionine, aspartate, aspartate (YMDD) mutants with or without additional compensatory mutations occur in chronically infected patients during lamivudine therapy and may be associated with accompanying viral breakthrough. The aim of this study was to determine whether a predominance of YMDD mutants could be a prognostic marker for occurrence of viral DNA breakthrough. YMDD genotypes in 740 consecutive samples collected from 116 patients throughout lamivudine treatment were retrospectively analyzed using a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)-based genotyping assay, termed restriction fragment mass polymorphism (RFMP). RFMP exploits differences in molecular masses between wild-type and variant bases of rtM204V/I following PCR amplification of HBV DNA with a lower limit of detection being 100 copies/mL. The study demonstrated that YMDD mutants occur throughout the course of lamivudine therapy irrespective of occurrence of viral DNA breakthrough, indicating that a mere detection of YMDD mutants could not sufficiently predict the viral DNA breakthrough, although presence of YMDD mutants is associated with high incidence of viral DNA breakthrou...Continue Reading

Citations

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