Abstract: Objective To evaluate mutations of HBV genes and explore the factors affecting mutations in Shanghai. Methods Detection data of gene mutations in HBV reverse transcriptase region (including sites at I169, V173, L180, A181, T184, A194, S202, M204, N236 and M250) of patients with chronic hepatitis B(CHB) in Shanghai Public Health clinical Center from 2015 to 2019 were collected, as well the consumptions of nucleoside (acid) medications (NAs) ; explore the factors influencing mutation out of gender, age, HBV DNA, glutamic oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), HBV sreological markers(HBVM) and genotype by univariate and multivariate analysis. Results 651 out of 4182 samples were detected mutations in HBV from 2015 to 2019, with a mutation rate of 15.57%; the mutation rate decreased along with the increasing consumptions of NAs with a higher genetic barrier year by year. Within 32 genetic mutation patterns of HBV in Shanghai, rtM204I, rtM204V+rtL180M and rtM204I+rtL180M were the dominant patterns with propotion of 32.41%, 29.33% and 16.44%, respectively; the rate of HBV resistant to lamivudine was the highest, followed by adefovir 2.13% and entecavir 0.22%, while no HBV resistant to tenofovir was found. Univariate analysis showed that age, genotype, ALT, AST, HBeAg and HBeAb were related to mutations, while multivariate analysis showed that age growth and HBeAb negative were risk factors of mutations. Conclusion 1. The genetic mutation rate of HBV decreased year by year from 2015 to 2019 in Shanghai, which may relate to the increasing consumptions of NAs with higher resistant barrier;2. HBV genetic mutation patterns are diversified with the dominant patterns of rtM204I, rtM204V+rtL180M and rtM204I+rtL180M; 3. The resistance rate of HBV to lamivudine is the highest; we should pay close attention to HBV resistant to entecavir in the future; 4. CHB patients who are older and HBeAb negative are more prone to mutate in HBV gene and resist to NAs.

Key words: Chroic hepatitis B, Hepatitis B virus, Genetic mutation, Resistance