Analysis in risk factors and gene mutation model of HBV polymerase region in patients with chronic hepatitis B after nucleoside analogues therapy

Objective To explore the variation in the gene mutation patterns and risk factors of HBV polymerase region (P) in chronic viral hepatitis (CHB) patients with nucleoside analogues therapy.Methods A total of 108 chronic hepatitis B patients with viral breakthrough after the treatment of nucleoside analogues were selected as the study subjects.The PCR product direct sequencing method was used to analyze the genetic variation of HBV P region.Results Among 108 cases,69 cases were detected by gene drug resistance,and the mutation type amount to 12,among which rtM204I was the most common (30.4％),and the second was rtL180M/rtM204I combined mutation (13％).The proportion of the major nucleoside analogues resistance highest proportion of lamivudine was 62.3％,followed by adefovir dipivoxil (21.7％) and telbivudine (15.9％).There were 33 cases with a single site mutation,29 cases with two sites mutation and 7 cases with three and above sites mutation.In the 7 cases,1 case was treated with lamivudine,1 case with entecavir,and the remaining 5 cases with irregular combined or sequential use of lamivudine,adefovir dipivoxil and entecavir.Conclusion The amino acid of HBV P gene resistant mutation is complex and varied,and rtM204V/I mutation is the most common type.Three and above sites mutation is associated with irregular combined or sequential use of lamivudine,adefovir dipivoxil and entecavir.