[Effect of hepatitis B virus preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B].

Objective: To explore the effect of HBV preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B. Methods: Thirty-five cases with chronic hepatitis B without antiviral therapy were enrolled in this cross-sectional study. Nested PCR-TA cloning-sequencing method was used to screen HBV preC/C and S gene mutation sites related to HBeAg serological status. Then, in the longitudinal study (60 cases), the independent correlation between HBV preC/C and S gene antigen epitopes mutations and HBeAg status was explored by using multiple regression models to correct the correlated confounding factors. Results: In this cross-sectional study, 64.4% of preC/C and 68.2% of S mutations had occurred in the epitope region. There were ten mutation sites (PreC/C50, 55, 79, 84, 103, 126, 145, 184 and s110, s213) correlated with HBeAg negative status (P < 0.05). After adjusting for confounding factors such as age, gender, HBV genotype, serum alanine aminotransferase level and precw28 * mutations in the longitudinal studies, the results showed that TC cell epitope (prec47-56, prec117-125, s208-216) and Th cell epitope (prec176-185) were the main independent risk factors affecting the host HBeAg serological status. Conclusion: HBV preC/C region (PreC47-56, PreC117-125 and PreC176-185) and S region (s208-216) epitope mutations are the main independent factors affecting the host HBeAg status, suggesting that these epitope mutations may be involved in the HBeAg seroconversion.目的： 探讨HBV PreC/C及S基因抗原表位的突变对慢性乙型肝炎患者HBeAg血清学状态的影响。 方法： 在横断面研究中，通过纳入35例未经抗病毒治疗慢性乙型肝炎患者，采用巢式PCR-TA克隆-测序方法筛选与HBeAg血清学状态相关的HBV PreC/C和S基因突变位点。然后在纵向研究中（60例）利用多元回归模型校正相关混杂因素，探讨HBV PreC/C及S基因抗原表位的突变与HBeAg状态之间的独立关系。 结果： 在横断面研究中，64.4%的PreC/C突变和68.2%的S突变发生在抗原表位区。有10个突变位点（PreC/C50、55、79、84、103、126、145、184和s110、s213）与HBeAg阴性状态相关（P < 0.05）。在纵向研究中校正了年龄、性别、HBV基因型、血清丙氨酸转氨酶水平和PreC W28*突变等混杂因素后，结果显示Tc细胞表位（PreC47-56、PreC117-125、s208-216）和Th细胞表位（PreC176-185）的突变是影响宿主HBeAg血清学状态的主要独立危险因素。 结论： HBV PreC/C区（PreC47-56、PreC117-125和PreC176-185）和S区（s208-216）表位的突变是影响宿主HBeAg状态的主要独立因素，提示这些抗原表位的突变可能参与HBeAg的血清学转换。.