持续病毒学应答与HCV感染者HCC发生风险关联性分析及证据质量评估

Association analysis of sustained virological response and HCC occurrence risk in HCV-infected patients and evidence quality evaluation

目的系统评价丙型肝炎治疗后病毒学应答与肝细胞癌发展之间的关联。方法制订meta分析的文献纳入和剔除标准,计算机检索MEDLINE(1966年—2017年12月)、EMbase(1980年—2017年12月)、Cochrane图书馆以及国内的中文科技期刊数据库、中国生物医学文献服务系统(1979年—2017年12月)等数据库,收集丙型肝炎患者治疗后持续病毒学应答与发生肝细胞癌关联的临床观察性研究。数据提取和文献质量评价由2名研究人员独立进行,文献质量采用纽斯卡尔-渥太华量表评价标准、专用软件RevMan 5.3.3对数据进行统计分析,采用GRADE pro version 3.6软件对合并后的证据质量进行综合评估。结果最终共纳入11项临床前瞻性队列研究,合计5763例患者。Meta分析结果显示:(1)丙型肝炎病毒感染者完成持续病毒学应答与发展成为肝细胞癌,以及与肝脏相关死亡之间关联分析的异质性检验结果分别为:(χ^2=19.01,I^2=47%)、(χ^2=3.38,I^2=0)。(2)符合标准的11项研究分析结果显示,丙型肝炎病毒感染者完成持续病毒学应答与降低患肝细胞癌的风险有关(相对危险度为0.22,95%CI为0.16—0.31),且为中等质量证据。(3)符合标准的7项研究分析结果显示,丙型肝炎病毒感染者完成持续病毒学应答与降低肝脏相关死亡率风险有关(风险比为0.15,95%CI为0.11—0.21),且为高质量证据。结论丙型肝炎病毒感染者任意阶段治疗后完成持续病毒学应答可减少肝细胞癌的发生和死亡,证据分别为中等和高级质量。

Objective To make a systematic review of the association between virological response and development of hepatocellular carcinoma after treatment with hepatitis C.Method The inclusion and exclusion criteria for reference entry were established.The source data from MEDLINE(1946 to Dec,2017),EMBASE(1980 to Dec,2017),the Cochrane Library,the Database of Chinese Biological and Medical(CBM)and the HTTP(1979 to Dec,2017)were extracted.These observational studies were systematically reviewed to compare therapy-derived sustained virologic response(SVR)with the development of HCC.Two investigators independently extracted data and evaluated the quality of evidence with the Newcastle-Ottawa Scale(NOS),statistical analysis was conducted with RevMan 5.3.3,and the quality of pooled evidence was determined with GRADE pro version 3.6 software.Result A total of 11 clinical prospective cohort studies were included,with a total of 5 763 patients.Meta analysis results showed that:(1)The heterogeneity test results of association analysis between HCV-infected individuals who completed SVR and developed liver cancer-related deaths were(χ^2=19.01,I^2=47%),(χ^2=3.38;I^2=0).(2)The results of 11 studies that met the criteria showed that the completion of SVR in HCV-infected individuals was associated with a reduced risk of HCC [relative risk(RR)0.22,95% CI:0.16-0.31],and evidence of moderate quality.(3)Seven studies that met the criteria showed that the completion of SVR in HCV-infected individuals was associated with a reduction in liver-related mortality risk [hazard ratio(HR)0.15,95% CI:0.11-0.21] and was of high quality.Conclusion The completion of SVR after treatment at any stage in HCV-infected patients may reduce the incidence and death of HCC,with evidence of moderate and advanced quality,respectively.