乙型肝炎病毒YMDD自然变异合并B、C基因型与乙型肝炎病毒相关肝细胞癌的关系  

The Correlation of Hepatocellular Carcinoma and Different Hepatitis B Virus Genotypes with Spontaneous YMDD Mutation

作　　者：陈学兵[1] 杨家红[1] 张浩[1] 陈皋[1] 王秀[1] 罗万蓉[1] 

机构地区：[1]德阳市人民医院感染科,四川德阳618000

出　　处：《华西医学》2015年第9期1650-1653,共4页West China Medical Journal

基　　金：四川省卫生厅科研课题(100175)~~

摘　　要：目的研究乙型肝炎病毒(HBV)YMDD自然变异合并B、C基因型与HBV相关肝细胞癌(HCC)的关系。方法纳入2010年5月-2012年5月收治的未经任何核苷(酸)类似物治疗的HBV相关HCC患者110例以及慢性HBV感染者1 079例(包括乙型肝炎携带者、慢性乙型肝炎、乙型肝炎肝硬化)。采用聚合酶链式反应(PCR)荧光杂交探针技术,通过DNA溶解温度值的差异区分血清HBV野生型和YIDD、YVDD两种耐药性突变株;采用型特异性探针Taqman荧光PCR技术检测血清HBV B、C型基因。根据不同资料类型分别采用t检验、χ2检验及非条件logistic回归分析进行统计学处理。结果在110例HBV相关HCC患者中,检测出HBV YMDD自然变异、C型基因及YMDD自然变异合并C型基因患者分别为16例(14.5%)、39例(35.5%)和14例(12.7%),而在1 079例慢性HBV感染者中,HBV YMDD自然变异、C型基因及YMDD自然变异合并C型基因患者分别为46例(4.3%)、153例(14.2%)和17例(1.6%),两组间差异均具有统计学意义(χ2=21.353,P<0.001;χ2=33.368,P<0.001;χ2=48.889,P<0.001)。非条件logistics回归分析表明,HBV C型基因感染者发生HCC的风险高于非C型基因[OR=2.943,95%CI(1.778,4.872),P<0.001];具有HBV YMDD自然变异合并C型基因特征的感染者发生HCC的风险高于不具有该特征的患者[OR=5.989,95%CI(2.394,14.980),P<0.001]。结论 HBV YMDD自然变异合并C型基因是慢性HBV感染者发生HBV相关HCC的独立危险因素,对早期筛查HBV相关HCC高危人群具有重要的临床应用价值。Objective To investigate the correlation of spontaneous YMDD mutation in different hepatitis B virus （HBV） genotypes with HBV-related hepatoceUular carcinoma （HCC）. Methods From May 2010 to May 2012, 110 HBV-related hepatocellular cancer patients not treated by anti-virus drugs and 1 079 chronic HBV infectors （including asymptomatic HBV carriers, chronic hepatitis B patients, and HBV-related liver cirrhosis patients） were included in our study. HBV YMDD mutation was detected by fluorescence hybridization bioprobe polymerase chain reaction （PCR） and melting curve assay using Diagnosis Kit for HBV YMDD Mutation （Qiagen Biotechnology）. Serum HBV genotype was detected by real time PCR using genotype specific TaqMan probe. According to data type, t-test, x^2-test and unconditional logistic regression were used for statistical analysis. Results In the HCC group, genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 39 patients （35.5%）, 16 patients （14.5%） and 14 patients （12.7%）, respectively. In the chronic HBV infection group, HBV genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 153 patients （14.2%）, 46 patients （4.3%） and 17 patients（1.6%）, respectively. The difference between the two groups were statistically significant （x^2=33.368, P 〈 0.001; ）x^2=21.353, P 〈 0.001; x^2=48.889, P 〈 0.001）. Unconditional logistic regression analysis suggested that infection of genotype C virus and genotype C virus with spontaneous YMDD mutation might be important risk factors for the development of HCC [OR=2.943, 95%CI （1.778, 4.872）, P 〈 0.001; OR=5.989, 95%CI （2.394, 14.980）, P 〈 0.001]. Conclusion Infection of genotype C virus with spontaneous YMDD mutation is tightly related with the occurrence of HCC and has important value for earlier warning of HCC.

关 键 词：乙型肝炎病毒 乙型肝炎病毒相关肝细胞癌 基因型 YMDD变异 

分 类 号：R512.62[医药卫生—内科学]