Sequence analysis of the HBV S protein in patients with chronic hepatitis B / 中华检验医学杂志

ABSTRACT

Objective To analysis the frequency and mutational patterns of HBV(hepatitis B virus) S protein in the different phases of chronic hepatitis B patients, exploring the clinical implication of these mutations in CHB. Methods The difference of S protein mutation rates and mutation site among each groups were analyzed by cases-comparison. 112 cases of chronic hepatitis B patients in Shanghai Shu-guang hospital were enrolled in this study; they were divided into four groups, immune-tolerance group [IT, 36 cases, male 20 cases,female 16 cases,age 28.00 (25.00,30.75)years], immune-clearance group [IC, 28 cases, male 17 cases,female 11 cases,age 29.00 (25.25,31.75) years], low-replication group [LR, 25 cases, male 17 cases,female 8 cases,age 39.00 (35.00,45.50) years], reactivation group [RE, 23 cases, male 15 cases,female 8 cases, age 43.00 (36.00, 48.00) years]. DNA sequencing was used to detection HBV S protein gene mutation. Difference between categorical variables were analyzed using Chi-square test, Non-parametric test (kruskal-wallis H and Mann-Whitney U) was used for non-normal distribution data. Results Naturally occurring MHR (major hydrophilic region) variants was 16.67％ (6/36 cases) in IT group, preferentially within"a"determinant in the first loop, compared with IC (21.43％,6/28 cases), LR (20.00％,5/25 cases) and RE (34.78％,8/23 cases), there was no statistics Significance (χ2=2.814, P=0.421), while variant frequencies outside the MHR were 11.11％ (4/36 cases) and 14.29％ (4/28 cases) in IT and IC group, viral diversity gradually increased during LR phase with 24.00％(6/25 cases) of mutation frequency, and peak at RE phase (52.17％, 12/23 cases) with a statistics significance (χ2=15.041, P=0.002). Conclusion Amino acid substitutions is not only the consequence of the pressure of host immunity, it may be a probably cause of disease reactivation.