不同评分模型对肝硬化患者经颈静脉肝内门体分流术后生存的预测价值

刘钰懿; 慕之勇; 胡辂; 王军; 熊伟; 胡鸿; 刘爱民; 安选; 许愈强; 余灏东; 王金能; 文良志; 陈东风

doi:10.3969/j.issn.1001-5256.2023.03.016

不同评分模型对肝硬化患者经颈静脉肝内门体分流术后生存的预测价值

DOI: 10.3969/j.issn.1001-5256.2023.03.016

刘钰懿¹,
慕之勇¹,
胡辂¹,
王军¹,
熊伟²,
胡鸿³,
刘爱民⁴,
安选⁵,
许愈强⁶,
余灏东⁷,
王金能⁸,
文良志¹,
陈东风^1, , ,

1.
陆军军医大学陆军特色医学中心(大坪医院) 消化内科，消化系统肿瘤精准防治重庆市重点实验室，重庆 400042
2.
重庆医科大学第三附属医院消化内科，重庆 400042
3.
川北医学院附属南充市中心医院介入放射科，四川南充 637000
4.
重庆大学附属涪陵医院消化内科，重庆 408000
5.
重庆大学附属三峡医院肝病科，重庆 404100
6.
乐山市人民医院消化内科，四川乐山 614000
7.
重庆大学附属黔江医院消化内科，重庆 409000
8.
重庆市第九人民医院消化内科，重庆 400042

基金项目:

国家自然科学基金 (82170594)

伦理学声明：本研究2022年4月19日已取得中国人民解放军陆军特色医学中心伦理委员会批准，批号：医研伦审(2022)第74号。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：刘钰懿、慕之勇、胡辂、王军负责调研整理文献，设计论文框架，撰写论文；王军、熊伟、胡鸿、刘爱民、安选、许愈强、余灏东，王金能、文良志负责研究方案设计，TIPS手术及结果分析解读；陈东风负责终审论文。

详细信息

通信作者:
陈东风，chendf1981@126.com (ORCID：0000-0001-5514-7358)

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出版历程
- 收稿日期: 2022-11-10
- 录用日期: 2022-12-29
- 出版日期: 2023-03-20

Value of different scoring models in predicting the survival of patients with liver cirrhosis after transjugular intrahepatic portosystemic shunt

1.
Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Army Specialized Medical Center of Army Medical University & Daping Hospital, Chongqing 400042, China
2.
Department of Gastroenterology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
3.
Department of Interventional Radiology, Nanchong Central Hospital, North Sichuan Medical College, Nanchong, Sichuan 637000, China
4.
Department of Gastroenterology, Chongqing University Fuling Hospital, Chongqing 408000, China
5.
Department of Hepatology, Chongqing University Three Gorges Hospital, Chongqing 404100, China
6.
Department of Gastroenterology, The People's Hospital of Leshan, Leshan, Sichuan 614000, China
7.
Department of Gastroenterology, Chongqing University Qianjiang Hospital, Chongqing 409000, China
8.
Department of Gastroenterology, The Ninth People's Hospital of Chongqing, Chongqing 400042, China

Research funding:

National Natural Science Foundation of China (82170594)

More Information

Corresponding author: CHEN Dongfeng, chendf1981@126.com (ORCID: 0000-0001-5514-7358)

摘要

摘要: 目的探讨Child-Pugh评分、终末期肝病模型(MELD)评分、联合血清钠离子的终末期肝病模型(MELD-Na)评分、慢性肝衰竭联盟-急性失代偿(CLIF-C AD)评分和经颈静脉肝内门体分流术(TIPS)术后生存Freiburg指数(FIPS)评分对肝硬化患者生存的预测价值。方法回顾性分析2014年1月—2021年2月我国西南地区多家医院行TIPS治疗的447例肝硬化患者的临床资料，其中生存组306例，死亡组62例。计算五种评分模型分值，并基于五种评分模型分别对患者进行生存分析。正态分布的计量资料组间比较采用独立样本的t检验；不符合正态分布的计量资料组间比较采用非参数Mann-Whitney U检验；计数资料组间比较采用Pearson χ²检验；采用Cox回归分析各评分模型对TIPS患者预后的影响；Kaplan-Meier法分析不同评分水平的患者死亡风险的差异，并采用Log-rank检验。各模型预测能力采用受试者工作特征曲线下面积(AUC)、不同时间点C指数及决策曲线进行评估。结果生存组患者年龄(Z=2.884)低于死亡组，Alb(t=3.577)、Na⁺(Z=-3.756)均高于死亡组，而酒精性肝硬化患者比例(χ²=22.674)、AST(Z=2.141)、PT(Z=2.486)、INR(Z=2.429)、TBil(Z=3.754)、腹水严重程度(χ²=14.186)及五种模型评分均低于死亡组(P值均＜0.05)。生存分析显示，各评分模型均能有效对TIPS患者预后进行风险分层。对各评分模型不同时间点C指数比较发现，Child-Pugh评分对术后生存预测能力较高，其次为MELD-Na评分、MELD评分和CLIF-C AD评分，而FIPS评分预测能力相对较差，此外，随时间延长，各评分预测效能均减弱。Child-Pugh评分术后1年生存率的预测效能最大(AUC=0.832)，MELD-Na评分术后3年生存率的预测效能最大(AUC=0.726)，而FIPS评分术后在1年和3年生存预测能力比较中均较差。结论五种评分模型均可作为肝硬化TIPS术后患者生存的预测方法，且都可为肝硬化TIPS患者提供有效的预后风险分层。在短期预测上Child-Pugh评分生存预测能力更好，长期预测上MELD-Na评分生存预测能力更好，而FIPS评分预测能力均相对较差。
- 肝硬化 /
- 门静脉高压 /
- 门体分流术, 经颈静脉肝内
Abstract: Objective To compare the value of Child-Pugh score, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, CLIF Consortium Acute Decompensation (CLIF-C AD) score, and Freiburg index of post-transjugular intrahepatic portosystemic shunt (TIPS) survival (FIPS) score in predicting the survival of patients undergoing TIPS. Methods A retrospective analysis was performed for the clinical data of 447 patients with liver cirrhosis who underwent TIPS in several hospitals in southwest China, among whom there were 306 patients in the survival group and 62 in the death group. The scores of the above five models were calculated, and a survival analysis was performed based on these models. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Pearson chi-square test was used for comparison of categorical data between groups; a multivariate Cox regression analysis was used for correction analysis of known influencing factors with statistical significance which were not included in the scoring models; the Kaplan-Meier method was used to evaluate the discriminatory ability of each model in identifying risks in the surgical population, and the log-rank test was used for analysis. The area under the receiver operating characteristic curve (AUC), C-index at different time points, and calibration curve were used to evaluate the predictive ability of each scoring model. Results Compared with the death group, the survival group had significantly lower age (Z=2.884, P < 0.05), higher albumin (t=3.577, P < 0.05), and Na⁺ (Z=-3.756, P < 0.05) and significantly lower proportion of patients with alcoholic cirrhosis (χ²=22.674, P < 0.05), aspartate aminotransferase (Z=2.141, P < 0.05), prothrombin time (Z=2.486, P < 0.05), international normalized ratio (Z=2.429, P < 0.05), total bilirubin (Z=3.754, P < 0.05), severity of ascites (χ²=14.186, P < 0.05), and scores of the five models (all P < 0.05). Survival analysis showed that all scoring models effectively stratified the prognostic risk of the patients undergoing TIPS. Comparison of the C-index of each scoring model at different time points showed that Child-Pugh score had the strongest ability in predicting postoperative survival, followed by MELD-Na score, MELD score, and CLIF-C AD score, and FIPS score had a relatively poor predictive ability; in addition, the prediction efficiency of each score gradually decreased over time. Child-Pugh score had the largest AUC of 0.832 in predicting 1-year survival rate after surgery, and MELD-Na score had the largest AUC of 0.726 in predicting 3-year survival rate after surgery, but FIPS score had a poor ability in predicting 1- and 3-year survival rates. Conclusion All five scoring models can predict the survival of patients with liver cirrhosis after TIPS and can provide effective stratification of prognostic risk for such patients. Child-Pugh score has a better ability in predicting short-term survival, while MELD-Na score has a better ability in predicting long-term survival, but FIPS score has a relatively poor predictive ability in predicting both short-term and long-term survival.
- Liver Cirrhosis /
- Portal Hypertension /
- Portasystemic Shunt, Transjugular Intrahepatic

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图 1 患者筛选流程图

Figure 1. Flowchart of the patient screening

下载: 全尺寸图片幻灯片

图 2 各评分模型多因素Cox回归分析森林图

注：a, 校正年龄、肝硬化病因和Na⁺后，Child-Pugh评分是TIPS患者预后的独立影响因素；b, 校正年龄、腹水、Alb和Na⁺后，MELD评分是TIPS患者预后的独立影响因素；c, 校正年龄、腹水和Alb后，MELD-Na评分是TIPS患者预后的独立影响因素；d, 校正肝硬化病因、腹水、Alb和TBil后，CLIF-C AD评分是TIPS患者预后的独立影响因素；e, 校正肝硬化病因、腹水、和Na⁺后，FIPS评分是TIPS患者预后的独立影响因素。

Figure 2. Forest plot of multifactor Cox regression analysis for each scoring model

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图 3 各评分模型内不同风险亚组患者生存曲线

Figure 3. Survival curves of patients in different risk subgroups within each scoring model

下载: 全尺寸图片幻灯片

图 4 各评分模型预测能力的比较

注：a, C指数；b, 决策曲线；c, 术后1年ROC曲线；d, 术后3年ROC曲线。

Figure 4. Comparison of prediction ability of each scoring model

下载: 全尺寸图片幻灯片

表 1 368例肝硬化患者临床资料基线特征

Table 1. Baseline characteristics of clinical data of 386 patients with liver cirrhosis

指标	所有患者(n=368)	生存组(n=306)	死亡组(n=62)	统计值	P值
年龄(岁)	52(45~60)	50(45~59)	56(49~66)	Z=2.884	0.004
性别[例(%)]				χ²=2.378	0.123
男性	263(70.9)	214(69.3)	49(79.0)
女性	105(29.1)	92(30.7)	13(21.0)
BMI(kg/m²)	22.9(21.0~24.9)	22.9(21.1-25.0)	22.7(20.8~24.7)	Z=-0.230	0.818
术前PVP(cmH₂O)	34(29~36)	34(30~36)	32(29~35)	Z=0.194	0.153
术后PVP(cmH₂O)	20(19~21)	20(19~20)	20(18~20)	Z=0.657	0.657
肝硬化病因[例(%)]				χ²=22.674	＜0.001
病毒性	267(71.4)	235(75.3)	32(51.6)
酒精性	42(11.9)	24(8.5)	18(29.0)
其他	59(16.7)	47(16.1)	12(19.4)
腹水量[例(%)]				χ²=14.186	0.001
无	155(41.8)	141(45.6)	14(22.6)
轻度	101(27.5)	83(27.2)	18(29.0)
中-重度	112(30.7)	82(27.2)	30(48.4)
WBC(×10⁹/L)	3.67(2.50~5.60)	3.59(2.49~5.54)	4.02(2.86~5.62)	Z=1.260	0.208
Hb(g/L)	83.0(68.5~100.0)	83.0(69.0~100.0)	82.0(68.0~106.0)	Z=-0.406	0.685
PLT(×10⁹/L)	61(43~90)	60(43~89)	61(43~101)	Z=1.030	0.303
Alb(g/L)	35.0±6.1	35.6±6.1	32.3±5.3	t=3.577	＜0.001
AST(U/L)	34.3(25.6~50.9)	33.7(25.3~47.6)	38.9(27.6~63.2)	Z=2.141	0.032
ALT(U/L)	26.3(18.8~38.1)	26.6(19.2~37.6)	22.5(16.3~41.9)	Z=-0.252	0.801
TBil(μmol/L)	24.4(17.9~33.8)	23.1(16.7~31.9)	29.5(22.5~49.3)	Z=3.754	＜0.001
Scr(μmol/L)	68.2(57.7~78.7)	68.3(58.0~77.1)	66.9(54.9~82.8)	Z=0.331	0.741
PT(s)	13.7(12.6~15.3)	13.6(12.5~14.9)	14.6(13.0~16.4)	Z=2.486	0.011
INR	1.19(1.09~1.33)	1.18(1.09~1.29)	1.29(1.13~1.43)	Z=2.429	0.015
Na⁺(mmol/L)	138.5(136.4~140.3)	138.9(137.2~140.4)	137.0(134.2~139.0)	Z=-3.756	＜0.001
Child-Pugh评分	7(6~8)	7(6~8)	8(7~9)	Z=4.374	＜0.001
MELD评分	10.2(8.4~12.1)	9.9(8.2~11.8)	11.3(9.8~14.6)	Z=-1.077	＜0.001
MELD-Na评分	12.4(10.6~14.4)	12.2(10.4~13.8)	14.3(12.0~16.6)	Z=0.378	＜0.001
CLIF-C AD评分	38.8(34.8~45.1)	38.3(34.3~44.5)	42.9(37.3~47.4)	Z=3.356	0.001
FIPS评分	-0.91(-1.35~-0.47)	-0.96(-1.40~-0.54)	-0.62(-1.00~-0.06)	Z=3.613	＜0.001
注：PVP，门静脉压。

下载: 导出CSV

表 2 单因素Cox回归分析结果

Table 2. Univariable Cox regression analysis for prognostic factors

项目	OR(95%CI)	P值	项目	OR(95%CI)	P值
年龄	1.047(1.022~1.072)	＜0.001	PLT	1.003(0.999~1.006)	0.185
BMI	0.982(0.907~1.063)	0.647	Alb	0.924(0.888~0.961)	＜0.001
性别	0.655(0.355~1.208)	0.176	AST	1.001(0.997~1.006)	0.562
PVP			ALT	0.998(0.992~1.005)	0.633
术前	0.976(0.924~1.030)	0.373	TBil	1.029(1.018~1.040)	＜0.001
术后	0.967(0.892~1.050)	0.426	Scr	1.002(0.990~1.013)	0.764
病因(病毒性比照)			PT	1.168(1.054~1.294)	0.003
酒精性	3.990(2.238~7.116)	＜0.001	INR	5.561(1.721~17.977)	0.004
其他	1.823(0.937~3.546)	0.077	Na⁺	0.907(0.863~0.953)	＜0.001
腹水(无腹水比照)			Child-Pugh评分	1.490(1.290~1.721)	＜0.001
轻度	2.096(1.042~4.216)	0.038	MELD评分	1.199(1.116~1.288)	＜0.001
中重度	3.865(2.043~7.314)	＜0.001	MELD-Na评分	1.195(1.122~1.273)	＜0.001
WBC	1.102(0.943~1.085)	0.748	CLIF-C AD评分	1.079(1.044~1.116)	＜0.001
Hb	0.998(0.988~1.009)	0.738	FIPS评分	2.168(1.495~3.144)	＜0.001

下载: 导出CSV

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