乙肝病毒C基因启动子变异与乙肝病情的关系

Clinical significance of mutation in the core promoter and the precore/core gene of hepatitis B virus in patients with chronic hepatitis B.

研究乙型肝炎病毒 (HBV)C基因启动子 (CP)变异与无症状慢性HBV携带者 (AsC)肝炎发作及与慢性乙肝病情的关系。通过PCR及其产物直接测序 ,检测 4例AsC、2 7例慢性乙肝和 3例慢性重型乙肝患者血清的HBVCP序列 ,并定量测定血清的HBVDNA。 (1)CP主要变异为nt172 6 - 1730聚集变异 (172 6A→C、172 7A→T、1730C→G)和nt176 2 176 4双变异 (176 2A→T和 176 4G→A)。 (2 )CP聚集变异与AsC首次肝炎急性发作有关。 11例中 ,8例出现CP聚集变异。且 1例在AsC状态时无CP变异 ,肝炎发作时出现CP聚集变异。 (3)CP聚集变异合并CP双变异的乙肝患者 ,表现为重型肝炎或迅速进展为肝硬化 ;HBVDNA高水平 ;HBeAg/抗HBe转换。CP聚集变异与AsC肝炎急性发作有关 ;CP聚集变异与CP双变异同时存在 ,使慢性乙肝病情加重。

To study the effects of mutations in the core promoter(CP)and the precore/core gene of hepatitis B virus (HBV) on acute clinical exacerbation in chronic asymptomatic HBV carriers (AsC) and the severity of patients with chronic hepatitis B. CP and precore/core gene were sequenced directly from sera of four AsCs, twenty-seven patients with chronic hepatitis B and three patients with chronic severe hepatitis B, after amplication by the polymerase chain reaction. Clusters of mutations in CP region, a A-to-C mutation at necleotide (nt) 1726, a A-to-T mutation at nt 1727 and a C-to-G mutation at nt 1730, were observed in eight of eleven AsCs developing acute exacerbation, Moreover, the clustering mutations were found negative in the state of AsC and positive after acute exacerbation in a subject. Five cases of the patients with both the clustering mutations and the double mutations (a A-to-T mutation at nt 1762 and a G-to-A mutation at nt 1764) manifested sever hepatitis or active cirrhosis with high level of serum HBV DNA and HBeAg/anti-HBe exchange. The clustering mutations are associated with acute exacerbation in HBV AsCs, and co-existence in the clustering mutations and the double mutations is related to the severity of chronic hepatitis B.