脾切除对病毒性肝炎肝硬化合并门静脉高压症患者肝癌发生影响的多中心队列研究

Effect of splenectomy on the risk of hepatocellular carcinoma development among patients with liver cirrhosis and portal hypertension:a multi-institutional cohort study

目的探讨脾切除术对肝硬化合并门静脉高压症患者发生肝细胞癌(HCC)的影响。方法回顾性收集2008年1月至2012年12月中国7所三级医院收治的因肝硬化和门静脉高压症继发脾功能亢进行脾切除术的407例患者的病例资料,纳入脾切除组;将同期因肝硬化和门静脉高压症接受药物治疗的464例患者的病例资料纳入非脾切除组。脾切除术中采用开腹或腹腔镜联合或不联合贲门血管离断术。非脾切除组中所有患者均在HCC发生前保守治疗肝硬化和门静脉高压症,未进行经颈静脉肝内门体分流术、脾切除或肝移植术。两组患者均采用相同的HCC监测方案。每3~6个月常规进行腹部超声检查、肝功能检查和甲胎蛋白检查。使用倾向性评分匹配(PSM)对脾切除组和非脾切除组的患者资料进行匹配。采用Kaplan-Meier法计算总体生存率和肝癌累积发生率,采用对数秩和检验比较两组患者的生存率。采用单因素和Cox比例风险回归模型分析影响肝癌发生的相关因素。结果PSM后,两组各233例患者。49例(12.0%)脾切除患者和75例(16.2%)非脾切除患者在随访期间发生了HCC。脾切除组患者1、3、5、7年HCC的累积发生率分别为1%、6%、7%、15%,显著低于非脾切除组1%、6%、15%、23%(HR=0.53,95%CI:0.31~0.91,P=0.028)。多因素分析结果显示,年龄≤40岁、男性、有脾切除史是HCC发生的独立相关因素(HR=0.55,95%CI:0.32~0.95,P=0.031)。脾切除组1、3、5、7年累积生存率分别为100%、97%、91%、86%,而非脾切除组为100%、97%、92%、84%,差异无统计学意义(P=0.899)。与非脾切除组的HCC患者相比,脾切除组发生HCC患者接受肝切除的比例更低(12.2%比33.3%,χ^(2)=7.029,P=0.008)。结论脾切除术可能降低肝硬化合并门静脉高压症患者HCC的发病风险。

Objective To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC)among patients with liver cirrhosis and hepatitis.Methods Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China,whereas patients receiving medication treatments for liver cirrhosis and portal hypertension(non-splenectomy)at the same time period among the seven hospitals were included as control groups.In the splenectomy group,all the patients received open or laparoscopic splenectomy with or without pericardial devascularization.In contrast,patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines(non-splenectomy)with no invasive treatments,such as transjugular intrahepatic portosystemic shunt,splenectomy or liver transplantation before HCC development.All the patients were routinely screened for HCC development with abdominal ultrasound,liver function and alpha-fetoprotein every 3 to 6 months.To minimize the selection bias,propensity score matching(PSM)was used to match the baseline data of patients among splenectomy versus non-splenectomy groups.The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development,and the Log-rank test was used to compare the survival or disease rates between the two groups.Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC.Results A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals.Among them,407 patients had a history of splenectomy for hypersplenism(splenectomy group),whereas 464 patients who received medical treatment but not splenectomy(non-splenectomy group).After PSM,233 pairs of patients were matched in adjusted cohorts.The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7%and 15%in the splenectomy group,which was significantly lower than 1%,6%,15%and 23%in the non-splenectomy group(HR=0.53,95%CI:0.31 to 0.91,P=0.028).On multivariable analysis,splenectomy was independently associated with decreased risk of HCC development(HR=0.55,95%CI:0.32 to 0.95,P=0.031).The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86%in the splenectomy group,which was similar with that of 100%,97%,92%,84%in the non-splenectomy group(P=0.899).In total,49 patients(12.0%)among splenectomy group and 75 patients(16.2%)in non-splenectomy group developed HCC during the study period,respectively.Compared to patients in non-splenectomy group,patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC(12.2%vs.33.3%,χ^(2)=7.029,P=0.008).Conclusion Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.