乙型肝炎病毒相关性肝内胆管细胞癌切除术患者的预后分析  

The prognosis analysis of hepatitis B virus-related intrahepatic cholangiocarcinoma patients after surgical resection

作　　者：于书敏 常秀娟 谷月月 贾晓东 黄加干 宫嫚 曾珍 Yu Shu-Min;Chang Xiu-Juan;Gu Yue-Yue;Jia Xiao-Dong;Huang Jia-Gan;Gong Man;Zeng Zhen(Peking University 302 Clinical Medical School,Beijing 100039,China;Department of Liver Disease Medicine,4Senior Department of Oncology,the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China;The 307 Clinical College of Chinese PLA/the Fifth School of Clinical Medicine,Anhui Medical University,Hefei,Anhui 230032,China;不详)

机构地区：[1]北京大学302临床医学院,北京100039 [2]解放军总医院第五医学中心肝病医学部,北京100039 [3]安徽医科大学解放军307临床学院/安徽医科大学第五临床医学院,安徽合肥230032 [4]解放军总医院第五医学中心肿瘤医学部,北京100039

出　　处：《解放军医学杂志》2024年第10期1134-1143,共10页Medical Journal of Chinese People's Liberation Army

基　　金：国家科技重大专项(2018ZX10725-506-002,2018ZX10302205-001)。

摘　　要：目的 探讨术前乙型肝炎病毒DNA(HBV-DNA)阴性的HBV相关性肝内胆管细胞癌(ICC)患者的预后。方法 收集2010年10月-2017年1月在解放军总医院第五医学中心接受手术切除的97例ICC患者的临床资料进行回顾性分析。将所有患者分为HBV相关性ICC(HBV-ICC)组(n=62)与非HBV相关性ICC(Con-ICC)组(n=35)。其中,HBV-ICC组包括HBV表面抗原阳性(HBsAg+)且HBV核心抗体阳性(HBcAb+)患者34例,HBsAg-且HBcAb+患者28例。采用Kaplan-Meier法绘制生存曲线,比较Con-ICC与HBV-ICC患者的总生存期(OS)和术后无复发生存期(RFS)差异,以及Con-ICC、HBsAg-/HBcAb+HBV-ICC与HBsAg+/HBcAb+HBV-ICC患者的OS和RFS差异;采用单因素和多因素Cox比例风险回归模型分析性别、年龄、致病因素、有无肝硬化、Child-Pugh分级、糖类抗原19-9(CA199)、甲胎蛋白(AFP)、谷氨酰胺转移酶(GGT)、碱性磷酸酶(ALP)、总胆红素(TBil)、直接胆红素(DBil)、美国癌症联合委员会(AJCC)分期、肿瘤大小、肿瘤数目、肿瘤分化、有无微血管侵犯、有无淋巴结转移、肝切除范围、有无胆囊切除和有无后续治疗等指标中影响患者OS、RFS及术后早期复发的因素。结果 97例中位年龄56岁,其中男79例(81.4%);中位随访时间92.2个月,其中88例(90.7%)复发,73例(75.3%)死亡。HBV相关病因及CA199>37 k U/L是ICC患者术后OS(HR=0.45,95%CI 0.26~0.77,P=0.003;HR=2.10,95%CI 1.24~3.57,P=0.006)、RFS(HR=0.43,95%CI 0.27~0.68,P<0.001;HR=1.78,95%CI 1.12~2.81,P=0.014)及早期复发(HR=0.42,95%CI 0.26~0.70,P=0.001;HR=2.02,95%CI 1.20~3.39,P=0.008)的独立影响因素。AJCC分期Ⅲ期是ICC术后RFS(HR=1.81,95%CI 1.04~3.14,P=0.037)的独立危险因素。多发肿瘤是ICC患者术后RFS及术后早期复发的独立危险因素(HR=1.73,95%CI 1.07~2.77,P=0.024;HR=1.90,95%CI 1.12~3.24,P=0.017)。HBsAg-/HBcAb+HBV-ICC患者与Con-ICC患者的OS、RFS及早期复发预后差异无统计学意义(P<0.05),而HBsAg+/HBcAb+是ICC患者术后OS(HR=0.32,95%CI 0.16~0.62,P=0.0Objective To investigate the prognosis of patients with hepatitis B virus(HBV)‐related intrahepatic cholangiocarcinoma(ICC)whose HBV DNA was negative before surgical.Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017.All patients were divided into HBV-related ICC(HBV-ICC)group(n=62)and non-HBV-related ICC(Con-ICC)group(n=35).HBV-ICC group included 34 patients with HBV core antigen positive(HBcAb+)and HBV surface antigen positive(HBsAg+),and 28 patients with HBcAb positive and HBsAg negative.Kaplan-Meier analysis was used to plot survival curves and compare the overall survival(OS)and postoperative recurrence-free survival(RFS)among patients in Con-ICC,ICC patients with HBsAg+/HBcAb+,and ICC patients with HBsAg-/HBcAb+.Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS,RFS and early postoperative recurrence among gender,age,pathogenic factor,liver cirrhosis,Child-Pugh grade,carbohydrate antigen 19-9(CA199),alpha-fetoprotein(AFP),glutamine transferase(GGT),alkaline phosphatase(ALP),total bilirubin(TBil),direct bilirubin(DBil),American Joint Committee on Cancer(AJCC)stage,tumor size,tumor number,tumor differentiation,microvascular invasion,lymph node metastasis,hepatectomy procedure,cholecystectomy,and follow-up treatment.Results Of the 97 patients,the median age was 56 years,and 79(81.4%)of them were male.The median follow-up time was 92.2 months.Eighty-eight(90.7%)patients presented with tumor recurrence and 73(75.3%)died.In multivariate analyses,HBV-ICC and CA199>37 kU/L were independent predictors of OS(HR=0.45,95%CI 0.26-0.77,P=0.003;HR=2.10,95%CI 1.24-3.57,P=0.006),RFS(HR=0.43,95%CI 0.27-0.68,P<0.001;HR=1.78,95%CI 1.12-2.81,P=0.014),and postoperative early recurrence(HR=0.42,95%CI 0.26-0.70,P=0.001;HR=2.02,95%CI 1.20-3.39,P=0.008).AJCC stageⅢwas an independent risk factor for p

关 键 词：肝内胆管细胞癌 乙型肝炎病毒 早期复发 预后 

分 类 号：R735.7[医药卫生—肿瘤]