C型HBV感染者发展为肝癌的危险因素及风险预测  

Risk factors analysis and a new risk scoring system predicting hepatocarcinogenesis for chronic genotype C HBV infected patients

作　　者：刘吉洛 蒲蕊[1] 马龙腾 王硕[1] 殷建华[1] 曹广文[1] Liu Jiluo;Pu Rui;Ma Longteng;Wang Shuo;Yin fianhua;Cao Guangwen(Department of Epidemiology,Second Military Medical University,Shanghai 200433,China)

机构地区：[1]第二军医大学流行病学教研室,上海200433

出　　处：《中华流行病学杂志》2018年第11期1459-1464,共6页Chinese Journal of Epidemiology

基　　金：国家重点基础研究发展计划（973计划）（2015CB554006）;国家自然科学基金（81373067）

摘　　要：目的 研究C型HBV感染者进展为肝癌的危险因素，构建相应的风险评估系统。方法 采用队列研究设计，对C型HBV感染者进行随访，采用巢式PCR技术检测HBV核心启动子区及PreS区的相关位点突变情况并进行分型。构建列线图模型，计算各项指标的风险系数并在验证队列中进行验证。结果 共纳入1 110例C型HBV感染者，平均随访8.52（5.36～11.68）年，肝癌发生率为11.93/1 000人年。在C型HBV感染者中，男性、年龄≥40岁、4种HBV核苷酸突变（T1674CG、A1762T/G1764A、A3120T和A2962G）可以增加肝癌发生的危险性（P〈0.05）；干扰素治疗可以降低肝癌发生的危险性（P〈0.05）。在此基础上构建风险评估体系，结果显示，预测与实际的病生存率拟合效果较好，预测值与实际值较相符，预测效果可信度较高。结论 C型HBV基因突变与肝癌发生关系密切。新构建的风险评估体系预测效果良好。Objective To investigate the effects of hepatitis B virus （HBV） genotype and mutations on the development of hepatocellular carcinoma （HCC） and to establish a new qualified HCC risk scores. Methods A cohort study enrolling patients with chronic HBV infection was conducted. HBV genotypes were identified by nested multiplex PCR. HBV mutations in the basic core promoter region and PreS region were sequenced after PCR amplification. Scores on risk factors were set based on nomogram. Results Totally, 1 525 patients were followed-up in this research. A total of 1 110 patients infected with genotype C were followed-up for 8.52 （QR：5.36-11.68） years on average, of whom the incidence of HCC was 11.93/1 000 person-years. In genotype C HBV infected patients, male gender, aged 40 years and over, and four DNA mutations （T1674CG, A1762T/G1764A, A3120T, and A2962G） can increase the risk of HCC （P〈0.05）; interferon therapy can reduce the risk of HCC （P〈0.05）. A new HCC predicting model was established according to the results. After validation, the predicted disease-free survival rate was consistent with the real one. Conclusions Hepatitis B virus genotypes and mutations were closely associated with HCC. The new risk scoring system can well predict HCC occurrence in genotype C HBV infected patients.

关 键 词：乙型肝炎病毒 肝肿瘤 基因型 

分 类 号：R735.7[医药卫生—肿瘤] R512.62[医药卫生—临床医学]