慢性重型乙型肝炎患者的乙型肝炎病毒C基因启动子和前C基因变异及与e抗原系统的关系

目的 研究慢性重型乙型肝炎患血清的HBV C基因启动子(CP)和前C基因变异情况。方法 通过DNA扩增、基因序列分析检测75例慢性乙型肝炎(CHB)和14例慢性重型乙肝(CSH)患血清的EIBV CP和前C基因序列，通过微粒子发光法定量检测血清中HBeAg的含量及通过荧光定量PCR技术定量检测血清中的HBV DNA。结果 (1)前C终止变异(nt1896G→A)在CASH组中的发生率显高于CHB组(71．4％和26．7％)；CP双变异(nt1762A→T和1764G→A)则在CASH组和CHB组的发生率无显差异(42．9％和48．0％)。(2)CSH组的HBeAg含量显低于CHB组；CSH组的HBeAb阳性率则显高于CHB组(71．4％和32．0％)。(3)CSH组和CHB组的HBV DNA定量则无明显差异。结论 前C终止变异，对e系统有明显影响，与CSH的发病有关。

Mutations in the core promotor and precore gene of hepatitis B virus in patients with chronic severe hepatitis B and their relationship with serum content of e antigen

Objective To study mutations in the core promoter(CP) and precore gene of hepatitis B virus(HBV)in patients with chronic severe hepatitis B and their relationship with serum content of e antigen.Methods CP and precore gene was sequenced directly from sera of 75 patients with chronic hepatitis B(CHB)and 14 patients with chronic severe hepatitis B(CSH),after amplification by the polymerase chain reaction.Results The double mutations in CP(A-to-T at nt 1762 and G-to-A at nt 1764)were observed in 36 of 75 patients with CH(48.0%)and in 6 of 14 patients with CSH(42.9%).Precore mutation(G-to-A at nt 1896)was observed in 20 of 75 patients with CH(26.7%)and in 10 of 14 patients with CSH(71.4%),the difference of which was significant.Content of e antigen from sera of patients with CP mutations and/or precore mutation was significantly lower than that of patients without the mutations.Patients with precore mutation significantly manifested HBeAg seroconversion.CP mutations and precore mutation did not significantly affect HBVDNA level.Conclusion Precore mutation and CP mutations decrease or block synthesis of HBeAg,and are related to the severity of chronic hepatitis B.Both kinds of mutations do not affect viral replication.