儿童肝移植术后肝纤维化的临床危险因素分析

目的研究儿童肝移植术后5年发生纤维化的临床相关危险因素。方法2013年1月至2016年12月天津市第一中心医院共完成儿童肝移植498例,其中94例于术后4~6年行肝穿刺活检。根据术后肝活检的结果将受者分为纤维化组和非纤维化组,采用单因素分析及多因素Logistic回归分析儿童肝移植术后肝纤维化临床危险因素。根据筛选出的独立危险因素建立Logistic回归模型,得到联合预测因子的预测值。绘制联合预测因子的受试者工作特征曲线(ROC),评价其预测纤维化发生的准确性。结果94例儿童受者中有54例(57.5%)出现肝纤维化。单因素分析显示,两组受者在冷缺血时间(Z=-2.094)、热缺血时间(Z=-2.421)、药物性肝损伤(χ²=7.389)、胆道狭窄(χ²=4.560)、肝动脉血栓、排斥反应(χ²=6.955)上差异有统计学意义(均P<0.05)。多因素Logistic回归分析显示冷缺血时间(OR=1.003,95%CI:1.000~1.006)、药物性肝损伤(OR=6.493,95%CI:1.615~26.101)、胆道狭窄(OR=6.451,95%CI:1.205~33.295)和排斥反应(OR=2.735,95%CI:1.057~7.077)是肝移植术后发生肝纤维化的独立危险因素。联合预测因子的ROC曲线下面积(AUC)为0.786(95%CI:0.691~0.881),临界值为0.311,灵敏度为90.70%,特异度为60.00%,且联合预测因子的诊断价值与其他独立危险因素单独诊断的价值差异有统计学意义(P<0.05)。结论儿童肝移植术后5年肝纤维化的发生率为57.5%,冷缺血时间、胆道狭窄、排斥反应和药物性肝损伤是儿童肝移植术后5年发生纤维化的独立危险因素。联合预测因子对儿童肝移植术后肝纤维化的发生具有较高的预测价值。

Analysis of the clinical factors related to fibrosis after pediatric liver transplantation

Objective To explore the clinicalfactors related to allograft fibrosis after pediatric liver transplantation.Methods The clinical data were respectively analyzed for 94 pediatric recipients from January 2013 to December 2016 at Tianjin First Central Hospital.The Patients were assigned into fibrotic and non-fibrotic groups based upon the results of protocol liver biopsies.Univariate and multivariate Logistic regression analyses were performed for examining the risk factors of fibrosis after pediatric livertransplantation.Then Logistic regression model was established to obtain the predicted value of combined predictive factors.Thereceiver operating characteristic curve(ROC)was conducted to evaluate the predictive value of combined predictive factors.Results A total number of 54(57.5%)patients occurred fibrosis among the 94 patients.There weresignificant differences in cold ischemia time(Z=2.094),warm ischemia time(Z=2.421),biliary stricture(χ²=4.560),drug-induced liver injury(χ²=7.389),hepatic artery thrombosis and rejection(χ²=6.955)between two groups(P<0.05).Logistic regression analysis showed that cold ischemia time(OR=1.003,95%CI:1.000~1.007,P=0.044),biliary stricture(OR=6.451,95%CI:1.205~33.295),rejection(OR=2.735,95%CI:1.057~7.077)and drug-induced liver injury(OR=4.977,95%CI:1.207~20.522,P=0.026)were independent risk factors for fibrosis 5 years after liver transplantation.The area under the ROC curve was 0.786(95%CI:0.691~0.881),for predicting patient outcome.If using 0.311as a cutoff Value,the sensitivity was 90.70%,and the specificity was 60.00%.However,through the ROC curve comparison,there was statistical significance between combined predictive factors and the other independent risk factors(P>0.05).Conclusions The incidence of fibrosis 5 years after pediatricliver transplantation is 57.5%.Prolonged cold ischemia time,biliarystricture,rejectionand drug-induced liver injury after liver transplantation are independent risk factors for fibrosis 5 years after pediatric liver transplantation.And the combined predictive factors have a high predictive value forallograftfibrosis.