Mutation Analysis Of The HBV Reverse Transcriptase In Nucleos(t)Ide-treatedpatients With Chronic HBV Infection

Objective: To characterize genotypic resistance within HBV RT region in chronic hepatitis B (CHB) patients with nucleos(t)ide analogue (NA) treatment in Tianjin.Methods:Serum samples of208CHB patients with NA treatment from Tianjin’s hospitals were obtained from December2010to August2012. Full-length HBV RT sequences were amplified, sequenced and analyzed, on the following NA resistant (NAr) mutations belonging to different NAr pathways: rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236and rtM250.Results:Among208Serum samples,203were positive for nested nPCR test and and were successfully sequenced.203HBV isolates,75(36.94%) harbored NAr mutations,14(18.67%) and,61(84.92%) were genotype B and C, respectively;6of11classical mutations were detected, and they are rtL80, rtV173, rtL180rtA181rtM204and rtN236, respectively. RtM204mutations (27rtM204I,15rtM204V and5rtM204I/V cases) were detected at the highest frequency among75mutants (49/75,65.33%) and found to display16combination mutation patterns. The frequency of the other5mutations was rtL80(23/75), rtV173(6/75), rtL180(28/75), rtA181(19/75), rtN236(5/75), respectively.Conclusion:36.94%of the studied population harbored NA HBV with complicated mutation patterns. Molecular analysis of HBV NA resistance mutations and concomitant HBsAg mutations is important for the surveillance of drug resistant and immune escape HBV mutants, for the diagnosis and treatment, and for the understanding of HBV pathogenicity.