HBsAg和抗HBs双阳性慢性HBV感染患者s区主要亲水区新增N-糖基化突变与肝细胞癌发生风险的相关性研究  

Risk association of hepatocellular carcinoma with S-gene additional N-glycosylation mutation of hepatitis B virus in HBsAg and anti-HBs coexistent patients

作　　者：乔艳[1,2] 许智慧[2] 卢姗姗[2] 李晓东[2] 黄鹏宇[2] 刘妍[2] 赵丽[2] 徐东平[2] 杨悦[2] 李进[3] 

机构地区：[1]桂林医学院研究生学院,广西桂林541004 [2]解放军第302医院临床研究管理中心,北京100039 [3]解放军第302医院医务部

出　　处：《解放军医学杂志》2016年第11期919-924,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81373136,81572010);首都卫生发展科研专项自主创新项目(2016-2-5032)~~

摘　　要：目的探讨临床HBsAg和抗HBs双阳性（简称双阳性）慢性HBv感染患者病毒S基因主要亲水区（MHR）新增N-糖基化突变与肝细胞癌（HCC）发生的相关性。方法纳入2009年7月-2015年6月在解放军302医院就诊的284例双阳性慢性HBV感染患者，通过巢式PCR方法扩增血清样本HBVs基因全序列并进行测序，分析MHR新增糖基化突变和其他临床指标与HCC发生的相关性并动态分析18例双阳性HCC患者临床确诊HCC前后S区新增N-糖基化的突变情况。结果多因素分析表明，患者年龄〉40岁、HBsAg〉中位数、HBeAg阴性和MRH新增N-糖基化突变是双阳性慢性HBV感染患者发展为HCC的危险因素（分别为OR=4．281，95％CI 1．843N9．941，P=0．001；OR=3．146，95％CI 1．633～6．060，P=0．001；OR=2．097，95％CI 1．010-4．357，P=0．047；OR=4．381，95％CI1．842—10．417，P=0．001），而丙氨酸氨基转移酶（AIT）、抗HBs〉中位数、抗HBe阳性和HBVDNA水平与HCC发生均无显著相关性。动态研究结果表明，18例双阳性HCC患者样本中有8例在发生HCC1-4年前已携有新增N．糖基化突变。结论在双阳性患者中HBVs基因MHR区新增N-糖基化突变与HCC发生密切相关，HBsAg和抗HBs双阳性叠加MH嘶增糖基化突变可作为慢性HBv感染患者HCC发生风险的预测指标。Objective To investigate the association of additional N-glycosylation mutation in major hydrophilic region （MHR） of hepatitis B virus （HBV） S gene with the risk of hepatocellular carcinoma （HCC） in HBsAg and anti-HBs coexistent patients. Methods A total of 284 patients with coexistence of HBsAg and anti-HBs were enrolled in this study, who were admitted in 302 Hospital of PLA from July 2009 to June 2016. HBV DNA was extracted from serum samples and subjected to nested PCR for full-length S-gene sequencing. The association of MHR additional N-glycosylation mutation and clinical parameters with HCC occurrence risk was analyzed. Specificall）5 the additional N-glycosylation mutation was dynamically analyzed pre- and post-HCC occurrence for 18 patients. Results Multivariate analysis showed that age 〉40 years, HBsAg 〉median, HBeAg negativity, and additional N-glycosylation mutation in MHRwere associated with HCC occurrence for the HBsAg and anti-HBs coexistent patients （OR=4.281, 95%CI 1.843-9.941, P=0.001; OR=3.146, 95%CI 1.633-6.060, P=0.001; OR=2.097, 95%CI 1.010-4.357, P=0.047; and OR=4.381, 95%CI 1.842-10.417, P=0.001）. In contrast, ALT, anti-HBs, anti-HBe, and HBV DNA levels had no significant association with HCC occurrence. Dynamical analysis showed that the additional N-glycosylation mutation had already developed 1-4 years prior to HCC occurrence in the 8 of 18 observed patients. Conclusion Additional N-glycosylation mutation in MHR of HBV S gene had close association with HCC occurrence in HBsAg and anti-HBs coexistent patients, suggesting that HBsAg and anti-HBs coexistence and additional N-glycosylation mutation together could serve as a predictive indicator for HCC occurrence in chronic HBV-infected patients.

关 键 词：肝炎 乙型 慢性 癌 肝细胞 突变 N-糖基化 

分 类 号：R735.7[医药卫生—肿瘤]