Abstract: Objective To investigate the association between hepatitis B virus (HBV) genotype and S protein mutations and to provide a theoretical basis for analyzing the role of viral genotype in the prognosis of disease.Methods Ninty-nine HBeAg negative chronic hepatitis B (CHB) patients admitted to our hospital from January 2019 to October 2019 were enrolled in this study, the number of genotype B and genotype C were 50 and 49, respectively. DNA sequencing was used to detect the gene sequence of HBV S protein. Differences between categorical variables were analyzed by Chi-square test and Continuity Correction. Non-parametric test (Mann-Whitney U) was used for analyzing non-normal distribution data.Results The mutation rate of S protein in genotype C group was significantly higher that of the genotype B group (87.76% vs.66.00% , χ²=6.567, P=0.010), furthermore, the mutation sites were distributed randomly, mutation rates in both major hydrophilic region (MHR) and outside the MHR of genotype C were higher than that of genotype B (38.78% vs.18.00%, χ²=5.266, P=0.022; 85.71% vs.56.00%, χ²=10.550, P=0.001 respectively). In addition, statistical differences were also found in the “a”determinant (32.65% vs.12.00% , χ²=6.107, P=0.013) located in MHR and immune epitopes (69.39% vs.40.00% , χ²=8.620, P=0.003) and nonimmune epitopes (53.06% vs.30.00%, χ²=5.424, P=0.020) of cytotoxic T lymphocytes + T-helper cell (CTL + Th ) located outside the MHR between the genotype C and B.Conclusion Genotype C was more prone to HBV S protein mutations than genotype B among HBeAg negative CHB patients.

Key words: Hepatitis B virus, S protein, Hepatitis B virus genotype, HBeAg negative chronic hepatitis B