经颈静脉肝内门体分流术治疗肝硬化顽固性腹水临床疗效及预后因素分析

Clinical effects and prognostic factors of transjugular intrahepatic portosystemic shunt in the treatment of refractory ascites

摘要:

目的：探讨经颈静脉肝内门体分流术（transjugular intrahepatic portosystemic shunt，TIPS）治疗肝硬化顽固性腹水的临床疗效及影响预后因素。方法：23例肝硬化顽固性腹水患者术后随访1~26月（平均9.7月），观察患者腹水缓解情况（腹水量）、临床血清学指标（血小板计数、白蛋白、总胆红素、凝血酶原时间、肌酐等）、生存率等。采用配对t检验、非参数检验分析术前术后临床血清学指标的变化情况，Kaplan-Merier方法计算生存率，术前危险因素预测3个月腹水疗效采用logistic回归分析，术前危险因素对术后生存情况的影响采用COX多因素回归模型分析，受试者工作曲线（receiver operating characteristic，ROC）及曲线下面积（area under the curve，AUC）判断最佳预测界值。结果：术后1年的各个随访期患者的腹水与术前比较明显改善，82.6%的患者术后1月腹水得到有效控制，52.4%患者在术后3月仅存少量腹水，术后6月在访的所有患者腹水均为少量。术后1周肝功能存在短期损害凝血酶原时间延长，中值（最小值，最大值）=19.6（14.0，28.7），Z=-2.419，P=0.016；Child-Pugh评分增加，x±s=9.87±1.71，t=-2.714，P=0.013；总胆红素升高，Z=-3.711，P=0.000，中值（最小值，最大值）=37.0（13.2，204.3），之后逐渐恢复。术后3个月、6个月及1年的累积生存率为95.5%、85.9%、78.1%。COX回归多因素分析显示血钠（P=0.027，HR=0.677，95%CI＝0.479～0.956）、总胆红素（P=0.007，HR=1.049，95%CI＝1.012～1.086）是影响预后的独立危险因素。运用ROC及AUC分析提示总胆红素AUC为0.676，95%CI为0.335~1.000，总胆红素37 μmol/L（敏感性66.7%，特异性94.1%）为最佳预测界值。Kaplan-Merier生存率分析显示总胆红素≥37 μmol/L及总胆红素＜37 μmol/L时的1年生存率分别为25%、92.3%。结论：TIPS是治疗肝硬化顽固性腹水的有效方案，术后存在短期的肝功能损害；总胆红素≥37 μmol/L是预测肝硬化顽固性腹水患者TIPS术后1年生存率的危险因素，可为术前判断患者预后提供临床依据。

Abstract:

Objective：To investigate clinical efficacy and prognostic factors of transjugular intrahepatic portosystemic shunt（TIPS） in the treatment of patients with refractory ascites. Methods：Totally 23 patients with consecutive postoperative refractory ascites were followed up for an average of 9.7 months（range from 1-26 month），and the remission of ascites，serum parameters（platelet，albumin，total bilirubin，creatinine，prothrombin time，etal），survival rate were observed. Paired t test and nonparametric test were used to ana－lyze the changes in clinical serological indexes before and after TIPS. The survival rate was calculated by Kaplan-Merier method. The preoperative risk factors were used to predict the therapy effect of ascites in three months by logistic regression analysis. Multiple factors COX regression was used to analyze the influence of preoperative risk factors on postoperative survival. ROC and AUC determined the best prediction value. Results：The ascites of patients during the first year after operation improved than those of pre-operation. The ascites of 19 patient（82.6%） were effectively controlled one month after operation. Thirteen patients（52.4%） and 23 patients（100%） had a small amount of ascites after 3 month and 6 month respectively. The hepatic functions were damaged in a short time about one week after TIPS，but gradually recoverd within the next month（prothrombin time prolonged，Z=-2.419，P=0.016，median（minimum，maximum）=19.6（14.0，28.7）；Child-Pugh scores increased，t=-2.714，P=0.013，x±s=9.87±1.71；total bilirubin rised，Z=-3.711，P=0.000，median（minimun，maximun）=37.0（13.2，204.3））. The 3 months，6 months and 1 year cumulative survival rate were 95.5%，85.9% and 78.1% respectively. COX regression analysis showed that serum bilirubin（P=0.007，HR=1.049，95%CI=1.012-1.086） and sodium levels（P=0.027，HR=0.677，95%CI=0.479-0.956） were independent risk factors associated with survival rate by using multi－variate analysis. According to ROC and AUC analysis，we selected the cut-off values of 37 μmol/L for serum bilirubin level（AUC=0.676，sensitivity=66.7%，specificity=94.1%，95%CI=0.335-1.000）. In addition，Kaplan-Meier survival analysis demonstrated that the one year cumulative survival in patients with serum bilirubin level <37 μmol/L was 92.3% as compared to 25% in patients with serum bilirubin level ≥37 μmol/L. Conclusion：TIPS is an effective programme of treatment for refractory ascites. The hepatic functions will be damaged in a short term after TIPS. The serum bilirubin level above 37 μmol/L is a prognostic factor of one year cumulative sur－vival in patients with cirrhosis and refractory ascites treated with TIPS，and which should be clinical basis for a judgment of prognosis.