血清HBV DNA前S/S区基因突变检测的回顾性临床应用研究

The Retrospective Clinical Study of the Detection of Mutations in PreS/S Gene Using Serum HBV DNA

目的探讨临床诊疗环境下,可疑病毒变异的慢性乙型肝炎患者群体中,血清HBV DNA前S/S区基因突变检测的潜在临床价值。方法按相应标准纳入189例于本院就诊且进行过前S/S区基因突变检测的、可疑病毒变异的慢性乙型肝炎患者,收集患者突变位点检测结果及临床资料。比较各位点突变检出率,不同肝病阶段、HBsAg/抗-HBs双阳性与HBsAg单阳性总突变检出率及各突变位点检出率的差异。并对137例肝炎及肝硬化患者进行随访,观察突变与肝病进展的关联。结果患者群体突变检出率为35.4%,且前S/S区突变主要位于“a”决定簇内,以第1环s126位点为著(20.6%)。肝炎、肝硬化及肝癌总突变检出率无明显差异,但肝癌患者PreS缺失突变检出率明显高于非肝癌患者(21.4%vs 4.0%,P=0.029),且只在肝癌患者中检出1例sT140I突变。而双阳组与单阳组突变检出率无明显差异。结论PreS缺失突变可能与肝癌发生有关;s126位点突变与免疫逃避有关,可导致乙肝慢性化及肝病进展。前S/S区突变检测对评估乙肝患者预后有一定价值,可用于联合评估肝病进展风险,拟定治疗方案及严格的随访策略,对防止或早期发现肝癌有一定临床价值。

Objective To explore the potential clinical value of serum HBV DNA pre-S/S gene mutation in chronic hepatitis B patients.Methods A total of 189 patients with chronic hepatitis B who had suspected viral mutations based on pre-S/S gene mutation detection results were included in the study.The detection results and clinical data of the patients were collected.The frequencies of each point mutation were compared.And the difference of the rates of mutation in patients with HBsAg/anti-HBs co-positive and HBsAg alone were also compared.137 patients were followed up,so to observe the association of mutation with the worse disease progression.Results The mutation rate of the population was 35.4%,and the mutation in the pre-S/S region was mainly located in the“a”determinant,especially in the s126 site of the first loop(20.6%).There were no significant differences in the rates of mutations among patients with hepatitis,cirrhosis and hepatocellular carcinoma(HCC).But the rate of PreS deletion mutation in patients with HCC was significantly higher than that in patients without HCC(21.4%vs 4.0%,P=0.029).And in patients with HCC,one case of sT140I mutation was detected.There was no significant difference in the rate of mutation between patients with HBsAg/anti-HBs co-positive and HBsAg alone.Conclusion PreS deletion mutation might be related to the development of HCC.And the mutation in s126 is related to immune escape,which could lead to the persistent and worse progressions.The detection of mutation in PreS/S region has certain value for evaluating the prognosis of CHB patients.It can be used to assess the risk of worse progression,and to formulate treatment and follow-up strategies for preventing or the early detection of HCC.