基于诺模图模型预测内镜下治疗肝硬化胃静脉曲张的疗效

目的通过诺模图(Nomogram)模型预测内镜下组织黏合剂治疗肝硬化患者胃静脉曲张的疗效。方法选择2014年8月至2017年9月因肝硬化食管胃底静脉曲张破裂出血至复旦大学附属中山医院就诊且接受内镜下组织黏合剂治疗的158例患者。随访12个月,主要结局指标为再出血。分析肝硬化胃静脉曲张内镜下治疗后再出血的影响因素。构建诺模图模型,比较其与Child分级、计算机体层摄影血管造影(CTA)和肝静脉压力梯度(HVPG)预测肝硬化胃静脉曲张内镜下治疗后再出血的准确性。统计学分析采用单因素和多因素Cox回归分析,以及Kaplan-Meier曲线和log-rank检验。结果随访中,在内镜下治疗后2、6和12个月分别出现再出血18例(11.4%)、37例(23.4%)和49例(31.0%)。单因素Cox回归分析结果显示,性别、酒精性肝硬化、糖尿病、Child-Pugh分级(A级与B或C级)、CTA腔外血管(有与无)、HVPG(<16 mmHg与≥16 mmHg,1 mmHg=0.133 kPa)、门脉系统广泛栓塞、食管静脉曲张、食管胃静脉曲张2型、组织黏合剂注射点(≤3点与>3点)和组织黏合剂注射量(≤3 mL与>3 mL)均为胃静脉曲张内镜下治疗后再出血的影响因素(HR=0.575、2.018、1.562、3.433、2.945、1.859、2.743、0.324、1.840、1.477、1.716,95%CI 0.305~1.084、0.902~4.514、0.814~2.792、1.753~6.724、1.663~5.217、1.012~3.415、0.852~8.830、0.079~1.335、1.012~3.317、0.839~2.602、0.935~3.152,P均<0.2)。多因素Cox回归分析结果显示,Child-Pugh分级、CTA腔外血管和HVPG均为胃静脉曲张内镜下治疗后再出血的独立危险因素(HR=2.665、2.886、2.095,95%CI 1.339~5.300、1.580~5.271、1.099~3.995,P均<0.05)。Kaplan-Meier曲线显示,Child-Pugh分级(A级与B或C级)、CTA腔外血管(有与无)和HVPG(<16 mmHg与≥16 mmHg)均能有效预测胃静脉曲张内镜下治疗后1年累积未再出血率,差异均有统计学意义(P均<0.05)。ROC曲线分析显示,联合Child-Pugh分级、CTA腔外血管和HVPG(<16 mmHg与≥16 mmHg)的模型可能比Child-Pugh分级和HVPG有更好的预测价值(AUC=0.746、0.673和0.585,95%CI 0.662~0.829、0.583~0.762和0.486~0.683,P<0.01、P=0.001、P=0.089)。根据诺模图评分的下四分位数和上四分位数将患者分为低、中、高危组,结果显示诺模图可以有效区分胃静脉曲张内镜下治疗后再出血的高危人群,差异有统计学意义(P<0.01)。结论CTA腔外血管、HVPG和Child-Pugh分级是肝硬化胃静脉曲张内镜下治疗疗效的独立预测指标,基于此3项指标建立的诺模图模型的预测准确性可能优于Child-Pugh分级和HVPG。

Prognostic Nomogram model for the efficacy of endoscopic treatment in gastric varices caused by liver cirrhosis

Objective To predict the efficacy of endoscopic tissue adhesives in the treatment of gastric varices in patients with liver cirrhosis by Nomogram model.Methods From August 2014 to September 2017,158 patients with liver cirrhosis caused esophagogastric variceal bleeding and received endoscopic tissue adhesives treatment at Zhongshan Hospital,Fudan University were collected.All patients were followed for 12 months.The primary outcome was rebleeding.The factors of rebleeding after endoscopic treatment of esophagogastric varices were analyzed.Nomogram prognostic model was developed and compared with Child-Pugh grading,computed tomography angiography(CTA)and hepatic venous pressure gradient(HVPG)in prognostic accuracy in rebleeding after endoscopic treatment in liver cirrhosis caused esophagogastric varices.Univariate and multivaricate Cox regression analysis,Kaplan-Meier curve and log-rank test were performed for statistical analysis.Results During the follow-up,rebleading occurred in 18 cases(11.4%),37 cases(23.4%)and 49 cases(31.0%)at 2,6,and 12 months after endoscopic treatment.The results of univariate Cox regression analysis showed the risk factors of rebleeding after endoscopic treatment of gastric varices included gender,alcoholic liver cirrhosis,diabetes mellitus,Child-Pugh grade(Grade A vs.B or C),extraluminal vessels on CTA(presence vs.absence)HVPG(<16 mmHg vs.≥16 mmHg,1 mmHg=0.133 kPa),extensive portal embolism,esophageal varices,type 2 gastric varices,injection points of tissue adhesive(≤3 points vs.>3 points),injection volume of tissue adhesive(≤3 mL vs.>3 mL)(hazard ratio(HR)=0.575,2.018,1.562,3.433,2.945,1.859,2.743,0.324,1.840,1.477,and 1.716;95%confidence interval(CI)0.305 to 1.084,0.902 to 4.514,1.753 to 6.724,1.663 to 5.217,1.012 to 3.415,0.852 to 8.830,0.079 to 1.335,1.012 to 3.317,0.839 to 2.602,and 0.935 to 3.152;all P<0.2).The results of multivariate Cox regression analysis indicated that Child-Pugh grade,extraluminal vessels by CTA,and HVPG(HR=2.095,95%CI 1.099 to 3.995,P=0.025)were all independent risk factors of rebleeding after endoscopic treatment of gastric varices(HR=2.665,2.886,and 2.095;95%CI 1.339 to 5.300,1.580 to 5.271,and 1.099 to 3.995;all P<0.05).Kaplan-Meier curves showed that Child-Pugh grade(Grade A vs.B or C),extraluminal vessels on CTA(presence or absent)and HVPG(<16 mmHg vs.≥16 mmHg)could effectively predict cumulative non-rebleeding rate in one year after endoscopic treatment of gastric varices,and the differences were statistically significant(all P<0.05).Receiver operataring characteristic curve analysis demonstrated that the predictive value of the model combined with Child-Pugh grade,extraluminal vessels on CTA and HVPG was higher than that of Child-Pugh grade and HVPG(AUC=0.746,0.673 and 0.585;95%CI 0.662 to 0.829,0.583 to 0.762,and 0.486 to 0.683;P<0.01,P=0.001 and P=0.089,respectively).Patients were divided into low,medium,and high-risk groups according to the 25th and 75th percentiles of the Nomogram score.The results showed that Nomogram model could effectively distinguish high-risk groups of rebleeding after endoscopic treatment of gastric varices,and the difference was statistically significant(P<0.01).Conclusions Extraluminal vessels on CTA,HVPG and Child-Pugh grade are independent prognostic evaluation indexes of rebleeding after endoscopic treatment of gastric varices.The predictive accuracy of Nomogram model based on these three prognostic factors may be better than Child-Pugh grade and HVPG.