乙肝相关疾病中乙肝病毒核心启动子区变异频率及发病风险评估  

Frequencies and risk of basic core promoter region mutations of HBV in HBV-related liver diseases

作　　者：张敏峰[1] 钱培新[2] 蒲蕊[3] 韩雪[4] 张宏伟[3] 杨甲梅[1] 殷建华[3] 

机构地区：[1]第二军医大学东方肝胆外科医院特需科,上海200438 [2]张家港市第一人民医院检验科,张家港215600 [3]第二军医大学流行病学教研室,上海200433 [4]上海市杨浦区疾病预防控制中心,上海200090

出　　处：《第二军医大学学报》2013年第9期929-933,共5页Academic Journal of Second Military Medical University

基　　金：上海市科委自然科学基金(13ZR1449000)~~

摘　　要：目的检测乙肝病毒核心启动子(basic core promoter,BCP)区变异位点在乙肝相关疾病中的变异频率,评估乙肝病毒变异在终末期肝病发生中的风险。方法收集2 093例HBV无症状携带者(asymptomatic HBsAg carrier,ASC)、慢性乙型肝炎(chronic hepatitis B,CHB)、肝硬化(liver cirrhosis,LC)和肝细胞癌(hepatocellular carcinoma,HCC)患者,应用测序法检测HBV位点变异;运用病例对照研究方法,以ASC组为对照,研究乙肝病毒核心启动子区的变异与乙肝相关疾病发生间的关系。应用非条件Logistic回归法分析校正年龄和性别后HBV变异在CHB、LC和HCC发生中的风险。结果 HCC组中除T1768A变异外,其余变异位点的变异频率均大于30%,而在ASC组中无变异位点的变异频率超过30%;7个变异位点在4组人群中变异频率均逐渐增高(Ptrend<0.001);除T1768A位点外,其余变异在CHB、LC和HCC组中的校正比值比(adjusted odds ratio,AOR)均逐渐增加,A1762T/G1764A双突变在HCC发生中的AOR为13.91(95%CI 9.66～20.03);HBV BCP区位点累积变异频率在乙肝相关疾病进展过程逐渐递增(Ptrend<0.001)。结论随着HBV BCP区变异在HBV相关肝病进展过程中逐渐累加,终末期肝病的发病风险增加;HBV BCP区变异可作为早期预测HBV相关终末期肝病发生的潜在分子标记物。Objective To evaluate the frequencies and risk of HBV mutations in basic core promoter （BCP） region in HBV-related liver diseases. Methods This case-control study enrolled a total of 2,093 cases, including asymptomatic HBV carriers （ASC）, chronic hepatitis B （CHB） patients, liver cirrhosis （LC） patients and hepatocellular carcinoma （HCC） patients. HBV mutations were detected by DNA sequencing method. The association of HBV mutations with the risks of CHB, LC, and HCC was evaluated by non-conditional Logistic regression model adjusted for age and sex as compared to ASCs. Results The frequencies of all the HBV mutations, except for T1768A mutation, in the HCC patients were higher than 30%; while all the HBV mutations frequencies were lower than 30% in ASCs. The frequencies of all the 7 HBV mutations gradually increased in ASCs, CHB, LC, and HCC groups in order （Ptrend〈0. 001）. The adjusted odds ratios （AOR） of all the HBV mutations, except for T1768A, were gradually increased in the CHB patients, LC patients, and HCC patients in order compared to ASCs. It was found that A1762T/G1764A was associated with HCC （AOR=13. 913 95% CI=9. 66-20. 03）. Thecumulative frequency of HBV mutations in the BCP region gradually increased with progression of hepatitis B related diseases （Ptrend〈0. 001）. Conclusion HBV mutation frequencies in the BCP region gradually accumulate during the progression HBV- related liver diseases, which finally leads to end-stage liver diseases. These HBV mutations can be used for early prediction of HBV-related end-stage liver disease.

关 键 词：乙型肝炎病毒 突变 肝肿瘤 肝细胞癌 慢性乙型肝炎 肝硬化 

分 类 号：R512.62[医药卫生—内科学]