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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (05) : 446 -452. doi: 10.3877/cma.j.issn.1674-1358.2018.05.006

所属专题： 文献；

论著

整合终末期肝病模型在慢加急性肝功能衰竭预后判断及治疗中的应用
蔡晓娟1, 沈毅2, 朱晓红1, 汪徐林2, 朱勇根1, 庄勋2, 秦刚1,†()   
  1. 1. 226006　南通市，江苏省南通市第三人民医院肝病中心
    2. 226019　南通市，南通大学公共卫生学院流行病与卫生统计教研室
  • 收稿日期:2018-03-01 出版日期:2018-10-15
  • 通信作者: 秦刚
  • 基金资助:
    江苏省重点研发（社会发展）计划重点病种规范化诊疗项目(No. BE2015655); 南通市市级临床医学中心项目(No. HS2016002)

Evaluation of integrated model for end-stage liver disease model in predicting prognosis of acute-on-chronic liver failure and the choice of treatment

Xiaojuan Cai1, Yi Shen2, Xiaohong Zhu1, Xulin Wang2, Yonggen Zhu1, Xun Zhuang2, Gang Qin1,†()   

  1. 1. Center for Liver Diseases, the Third People’s Hospital of Nantong, Nantong 226006, China
    2. Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong 226019, China
  • Received:2018-03-01 Published:2018-10-15
  • Corresponding author: Gang Qin
  • About author:
    Corresponding author: Qin Gang, Email:
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引用本文：

蔡晓娟, 沈毅, 朱晓红, 汪徐林, 朱勇根, 庄勋, 秦刚. 整合终末期肝病模型在慢加急性肝功能衰竭预后判断及治疗中的应用[J]. 中华实验和临床感染病杂志(电子版), 2018, 12(05): 446-452.

Xiaojuan Cai, Yi Shen, Xiaohong Zhu, Xulin Wang, Yonggen Zhu, Xun Zhuang, Gang Qin. Evaluation of integrated model for end-stage liver disease model in predicting prognosis of acute-on-chronic liver failure and the choice of treatment[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(05): 446-452.

目的

探讨整合终末期肝病模型(iMELD)评分系统对慢加急性肝功能衰竭(ACLF)患者近期与远期预后的判断价值，及其对人工肝治疗选择的指导意义。

方法

回顾性分析2003年1月至2007年12月江苏省南通市第三人民医院收治的232例乙型肝炎慢加急性肝功能衰竭(HBV-ACLF)患者队列的临床资料，其中生存组83例，死亡组149例。根据基线肝肾功能、电解质、凝血酶原时间和并发症等，计算终末期肝病模型(MELD)、MELD-Na、integrated MELD(iMELD)、Child-Turcotte-Pugh评分(CTP)、改良Child评分(mCTP)5种模型评分；随访两组患者90 d的生存率。分别从鉴别力、校准度和整体性能3个方面评价5种评分系统预后预测的准确性；探讨单指标血浆凝血酶原活动度(PTA)和此5种模型在文献报道的临界值指导下对患者选择人工肝治疗的准确性和可靠性，用决策曲线分析(DCA)方法计算各个模型及"全治疗"策略的净获益，评价模型对预测疗效的临床意义。

结果

MELD、MELD-Na、iMELD、CTP、mCTP 5种评分系统均能较好利用数据信息，且与ACLF患者预后有显著相关性；在判断患者90 d预后时，受试者工作特征曲线下面积(AUC)分别为0.63、0.64、0.68、0.62和0.64；iMELD均优于其他评分系统(t = 8.318、P <0.001)；iMELD评分的最佳临界值具有最好的病死风险判断力；Nagelkerke’s R2和Brier评分结果提示iMELD整体判断能力最优。以55为界值，iMELD短期预后判断能力的敏感度为86.8%，特异度为49.5%，AUC = 0.68；iMELD预测能力优于PTA单指标(t= 5.866、P <0.001)以及其他模型；阈值概率(Pt)为23%～65%时，基于iMELD评分决定是否应用人工肝治疗，净获益高于"全治疗"策略，相当于每100例患者中可减少不必要的人工肝治疗最多达20例，提示使用iMELD模型指导可节约20%的人工肝资源，同时亦不增加漏掉需要人工肝治疗患者的几率。

结论

iMELD模型在判断ACLF患者近期与远期预后方面的价值较高，对临床选择合适病例进行人工肝支持系统治疗具有指导意义。

关键词: 肝功能衰竭，慢加急性, 肝炎病毒，乙型, 预后模型, 决策曲线分析
Objective

To investigate the predictive value of integrated model for end-stage liver disease (iMELD) scoring system for short-term and long-term prognosis of (ACLF) patients with chronic and acute hepatic failure and its guiding significance for the selection of artificial liver support system (ALSS).

Methods

From January 2003 to December 2007, the clinical data of 232 patients with chronic hepatitis B and acute hepatic failure (HBV-ACLF) in the Third People’s Hospital of Nantong were analyzed, retrospectively, who were divided into survival group (83 cases) and death group (149 cases). According to the baseline of liver and kidney function, the electrolytes, prothrombin time and complications, the scores of the model for end-stage liver disease (MELD), MELD-Na, integrated MELD (iMELD), Child-Turcotte-Pugh (CTP) and modified CTP (mCTP) were calculated, respectively. The survival rates of 90 d and 5 years were compared between the two groups during the follow-up. The accuracy of prognostic prediction of the five scoring systems was evaluated from three aspects: discriminant ability, calibration degree and overall performance. The accuracy and reliability of selecting artificial liver treatment of single index plasma prothrombin activity (PTA) and the five models under the guidance of critical value reported in literature were investigated. The net benefit of each model and "total therapy" strategy was calculated by the decision curve analysis (DCA) method, and the clinical significance of the model in predicting curative effect were evaluated.

Results

MELD, MELD-Na, iMELD, CTP and mCTP scoring systems could make good use of data information and have a significant correlation with the prognosis of ACLF patients. The area under the receiver operating characteristic curve (AUC) for these models were 0.63, 0.64, 0.68, 0.62 and 0.64 for 90-day survival and 0.65, 0.71, 0.80, 0.78 and 0.78 for 5-year survival, respectively. IMELD was superior to other scoring systems (t= 8.318,P< 0.001). The best critical value of iMELD score has the best judgment of death risk. Nagelkerke’s R2and Brier scores indicated that iMELD had the best overall judgment ability. With 55 as the threshold, the sensitivity and specificity of short-term prognostic judgement of iMELD were 86.8% and 49.5%, respectively; AUC = 0.68. The predictive ability of iMELD was superior to that of single index of PTA (t= 5.866,P< 0.001). When the threshold probability (Pt) was 23%-65%, the net benefit of artificial liver therapy based on the iMELD score was higher than that of the "total treatment" strategy, equivalenting of reduce unnecessary artificial liver therapy to up to 20 cases per 100 patients. It is suggested that the use of iMELD model could save 20% of artificial liver resources, and not increase the probability of missing out the patients who need artificial liver treatment.

Conclusions

Integrated MELD model may be the best model to predict short-term and long-term prognosis in patients with ACLF, which may have clinical implications for diagnosis and treatment.

Key words: Acute-on-chronic liver failure, Hepatitis B virus, Model for end-stage liver disease, Decision curve analysis
图1 HBV-ACLF患者ALSS治疗决策树
表1 HBV-ACLF生存组和死亡组患者的基线资料
临床指标 生存组(83例) 死亡组(149例) 统计量 P值
男/女(例) 64/19 114/35 χ2 = 0.011 0.918
年龄(±s，岁) 41.4 ± 10.2 48.7 ± 9.8 t = 5.364 < 0.001
HBeAg阳性[例(%)] 47(20.2) 95(40.9) χ2 = 1.142 0.285
TBil(±s，μmol/L) 189 ± 69 240 ± 98 t = 4.207 < 0.001
肌酐(±s，mg/L) 0.8 ± 0.2 1.0 ± 0.9 t = 2.532 0.012
PT(±s，s) 32.7 ± 10.7 43.4 ± 1.4 t = 5.274 < 0.001
PTA(±s，%) 21.1 ± 8.0 15.2 ± 7.0 t = 5.866 < 0.001
白蛋白(±s，g/L) 33.8 ± 4.7 31.1 ± 4.8 t = 3.988 < 0.001
Na(±s，mmol/L) 137.0 ± 5.7 129.2 ± 9.2 t = 7.037 < 0.001
肝硬化[例(%)] 20(8.6) 92(39.7) χ2 = 30.259 < 0.001
腹水[例(%)] 54(23.3) 140(60.3) χ2 = 32.505 < 0.001
肝性脑病[例(%)] 7(3.0) 57(24.6) χ2 = 23.731 < 0.001
肝肾综合征[例(%)] 0(0.0) 37(15.9) χ2 = 24.522 < 0.001
诊断分期[例(%)] ? ? χ2 = 33.477 < 0.001
? 早期 12 (5.2) 6 (2.6) ? ?
? 中期 37(15.9) 26(11.2) ? ?
? 晚期 34(14.7) 117(50.4) ? ?
MELD(±s，分) 27.2 ± 4.6 30.0 ± 5.5 t = 3.985 < 0.001
MELD-Na(±s，分) 28.3 ± 4.4 32.0 ± 4.9 t = 5.618 < 0.001
iMELD(±s，分) 43.7 ± 7.3 54.2 ± 10.1 t = 8.318 < 0.001
CTP(±s，分) 10.5 ± 1.6 12.2 ± 1.4 t = 8.286 < 0.001
mCTP( ±s，分) 13.1 ± 2.0 15.1 ± 1.6 t = 8.307 < 0.001
图2 HBV-ACLF患者90 d累积生存率
表2 根据模型临界值预测HBV-ACLF患者3个月结局
模型 临界值 敏感度(%) 特异度(%) PPV(%) NPV(%) AUC(95%CI) DOR(95% CI)
PTA 30% 39.70 77.50 65.80 54.10 0.59(0.53～0.64) 2.26(1.28～4.01)
MELD 30分 70.20 55.00 63.00 62.90 0.63(0.56～0.69) 2.88(1.68～4.93)
iMELD 55分 86.80 49.50 65.20 77.50 0.68(0.63～0.74) 6.45(3.4～12.2)
MELD-Na 30分 56.20 71.20 64.50 66.00 0.64(0.58～0.70) 3.17(1.84～5.45)
CTP 10分 24.80 99.10 96.80 54.70 0.62(0.58～0.66) 10.4(4.71～22.8)
mCTP 16分 78.50 49.50 62.90 67.90 0.64(0.58～0.70) 3.59(2.03～6.34)
图3 预测HBV-ACLF患者人工肝治疗净获益的决策曲线
表3 ACLF患者全治疗净获益以及运用Pt在iMELD指导下的净获益
Pt (%) 净获益 iMELD指导下人工肝的优势
全治疗 仅治疗iMELD< 55者 净获益 每100例患者减少不必要人工肝的患者例数
23 0.379 0.380 0.001 1
30 0.317 0.349 0.032 8
40 0.203 0.292 0.089 13
50 0.043 0.211 0.168 17
60 －0.196 0.091 0.287 19
65 －0.367 0.004 0.371 20
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