直接抗病毒药物清除HCV后肝细胞肝癌发生风险因素的调查研究  

Investigation on risk factors of hepatocellular carcinoma after the eradication of HCV with direct-acting antiviral agents therapy

作　　者：纪冬 熊艺茹 李冰 李忠斌 牛小霞 邵清 陈国凤 JI Dong;XIONG Yi-ru;LI Bing;LI Zhong-bin;NIU Xiao-xia;SHAO Qing;CHEN Guo-feng(Second Liver Cirrhosis Diagnosis and Treatment Center,the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China)

机构地区：[1]中国人民解放军总医院第五医学中心肝硬化诊疗二中心,北京100039 [2]河北一洲肿瘤医院六病区,涿州072750

出　　处：《传染病信息》2019年第4期317-321,共5页Infectious Disease Information

基　　金：中华医学会临床医学科研专项基金(13071110496);首都临床特色应用研究特色课题(Z181100001718034)

摘　　要：目的通过前瞻性队列研究,探索慢性丙型肝炎(chronic hepatitis C,CHC)患者接受直接抗病毒药物(directacting antiviral agents,DAAs)治疗获得持续病毒学应答(sustained virologic response,SVR)后肝细胞肝癌(hepatocellularcarcinoma,HCC)发生的高危因素,为HCC的精准诊疗提供依据。方法以2015年10月起来我中心就诊的、符合抗病毒治疗指征的CHC患者为研究对象,采用全口服DAAs治疗12~24周,以获得SVR(定义为停药12周后HCV RNA低于最低检测下限)为进入队列的起始时间,之后每12周进行1次随访,通过腹部彩超及AFP对HCC进行监测,终点为明确HCC诊断(增强核磁共振或肝活检)。采用COX比例风险模型分析HCC相关高危因素。结果最终纳入506例患者,46.2%(234例)为男性,平均年龄(49.1±11.8)岁、身体质量指数(23.7±3.3)kg/m2、HCV RNA定量为(6.1±1.2)log10 IU/ml,肝硬化患者占16.2%(82例),基因1b型占73.3%(371例),中位随访时间36.6个月,HCC的累积1、2、3年新发率分别为1.2%、3.5%、5.9%。COX比例风险模型分析提示合并糖尿病、年龄≥55岁、血小板低于正常值下限以及合并肝硬化(LSM>17.5 kPa)为HCC新发的高危因素。结论DAAs治疗不能完全避免HCC的发生,获得SVR后仍须对具有高危因素的个体进行严密的HCC监测。Objective To explore the high risk factors associated with hepatocellular carcinoma(HCC)in patients with chronic hepatitis C(CHC)who achieved sustained virologic response(SVR)after direct-acting antiviral agents(DAAs)therapy through a prospective cohort study,and to provide basis for accurate diagnosis and treatment of HCC.Methods CHC patients who were admitted in our center after October 2015 and complied with the indications of antiviral therapy were included in this study.The initial time point of enrolling the cohort was the achievement of SVR(defined as HCV RNA under the lower limit of quantification at 12 weeks after completion of the DAAs therapy)after receiving pan-oral DAAs therapy for 12-24 weeks.Subsequently patients were followed up at 12 weekly intervals with surveillance for HCC performed by alpha-fetoprotein and ultrasonography at each visit.The end-point was the definitive diagnosis of HCC(enhanced MRI scan or liver biopsy).COX proportional hazard model analysis was used to analyze high-risk factors associated with HCC.Results Finally 506 patients were enrolled,46.2%(234 cases)of them were male.The average age was(49.1±11.8)years.Body mass index was(23.7±3.3)kg/m2.HCV RNA level was(6.1±1.2)log10 IU/ml.The percentages of patients who had liver cirrhosis or genotype 1b HCV infection were 16.2%(82 cases)and 73.3%(371 cases)respectively.The median follow-up duration was 36.6 months.The 1-,2-,3-year cumulative occurrence rates of HCC were 1.2%,3.5%,5.9%,respectively.COX proportional hazard model analysis showed that complication with diabetes mellitus,age≥55 years,platelet under the lower limit of normal value and complication with liver cirrhosis(LSM>17.5 kPa)were high risk factors associated with new HCC occurrence.Conclusions DAAs therapy can not completely avoid the occurrence of HCC.Post-SVR HCC surveillance is suggested for individuals at high risk.

关 键 词：慢性丙型肝炎 直接抗病毒药物 肝细胞肝癌 高危因素 

分 类 号：R516.7[医药卫生—内科学]