血清肠型脂肪酸结合蛋白（I-FABP）在慢加急性肝衰竭发生发展中的预测价值

韩才均; 朴美花; 黄媛; 吴政燮; 金星; 李光一

doi:10.12449/JCH240820

血清肠型脂肪酸结合蛋白（I-FABP）在慢加急性肝衰竭发生发展中的预测价值

DOI: 10.12449/JCH240820

韩才均^a,
朴美花^a,
黄媛^b,
吴政燮^a,
金星^c,
李光一^d, , ,

a.
延边大学附属医院检验科，吉林延吉 133000
b.
延边大学附属医院消化内科，吉林延吉 133000
c.
延边大学附属医院感染科，吉林延吉 133000
d.
延边大学附属医院肝胆外科，吉林延吉 133000

基金项目:

延边大学应用基础项目 (YDKJ202327);

延边大学应用基础项目 (YDKJ202445)

伦理学声明：本研究方案于2020年12月8日经由延边大学附属医院伦理委员会审批，批号：2020-211。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：韩才均负责课题设计，资料分析，撰写论文；黄媛、吴政燮、金星参与收集数据，病例资料分析和修改论文；朴美花、李光一拟定写作思路，并最后定稿。

详细信息

通信作者:
李光一， 1026481986@qq.com （ORCID： 0000-0002-6603-5244）

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出版历程
- 收稿日期: 2023-12-24
- 录用日期: 2024-02-21
- 出版日期: 2024-08-25

Value of intestinal fatty acid binding protein in predicting the development and progression of acute-on-chronic liver failure

a.
Department of Medical Laboratory, The Affiliated Hospital of Yanbian University，Yanji，Jilin 133000，China
b.
Department of Gastroenterology, The Affiliated Hospital of Yanbian University，Yanji，Jilin 133000，China
c.
Department of Infectious Diseases,The Affiliated Hospital of Yanbian University，Yanji，Jilin 133000，China
d.
Department of Hepatobiliary Surgery，The Affiliated Hospital of Yanbian University，Yanji，Jilin 133000，China

Research funding:

Applied Foundation Research Project of Yanbian University (YDKJ202327);

Applied Foundation Research Project of Yanbian University (YDKJ202445)

More Information

Corresponding author: LI Guangyi， 1026481986@qq.com （ORCID： 0000-0002-6603-5244）

摘要

摘要: 目的探讨血清肠型脂肪酸结合蛋白（I-FABP）对慢加急性肝衰竭（ACLF）发生发展的预测作用。方法回顾性分析2020年9月—2023年3月延边大学附属医院收治的168例肝硬化失代偿患者的临床资料，观察入院合并ACLF的患者情况和随访6个月新发ACLF事件。采用ELISA法测定患者入院血清I-FABP水平。非正态分布计量资料两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H秩和检验。计数资料组间比较采用χ²检验。趋势性分析采用Jonckheere-Terpstra检验。采用Spearman相关分析两变量间相关性。多变量Cox回归法分析随访期间新发ACLF的影响因素。Kaplan-Meier曲线分析不同组间ACLF发生情况，并采用Log-rank检验评估差异。采用受试者工作特征曲线（ROC曲线）和曲线下面积评估I-FABP对ACLF发生、发展的预测性能。结果入组168例患者中43例合并ACLF，125例无ACLF的患者在随访期间新发ACLF19例。纳入时合并ACLF患者的I-FABP水平高于无ACLF者，差异有统计学意义（Z=4.359，P<0.001）。新发ACLF患者的I-FABP水平均高于未发生ACLF者，差异有统计学意义（Z=3.414，P<0.001）。I-FABP随ACLF分级增加而升高（H=17.385，P<0.001，P_趋势<0.001）。多因素分析显示I-FABP与随访期间新发ACLF独立相关（HR=2.138，95%CI：1.297～3.525，P=0.003），且I-FABP三分位数显示出良好的区分能力（χ²=12.16，P<0.001）。ROC曲线显示I-FABP对ACLF发生和发展具有较好的预测效能，ROC曲线下面积分别为0.854（95%CI：0.791～0.903）和0.747（95%CI：0.661～0.820），最佳截断值分别为2.07 μg/L和1.86 μg/L。结论 I-FABP是预测ACLF发生和发展的生物标志物，有助于临床识别高危患者，改善临床管理。
- 慢加急性肝功能衰竭 /
- 肠脂肪酸结合蛋白质类 /
- 生物标记
Abstract: Objective To investigate the value of intestinal fatty acid binding protein （I-FABP） in predicting the development and progression of acute-on-chronic liver failure （ACLF）. Methods A retrospective analysis was performed for the clinical data of 168 patients with decompensated liver cirrhosis who were admitted to The Affiliated Hospital of Yanbian University from September 2020 to March 2023. The conditions of the patients with ACLF on admission were observed， and the patients were followed up for 6 months to identify new-onset ACLF cases. ELISA was used to measure the serum level of I-FABP on admission. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H rank sum test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups； the Jonckheere-Terpstra test was used for trend analysis. The Spearman correlation analysis was used to investigate the correlation between two variables， and the multivariate Cox regression analysis was used to investigate the influencing factors for new-onset ACLF during follow-up. The Kaplan-Meier curve was used to analyze the onset of ACLF in different groups， and the log-rank test was used for the analysis of such differences. The receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to investigate the performance of I-FABP in predicting the development and progression of ACLF. Results Among the 168 patients enrolled in this study， there were 43 patients with ACLF and 125 patients without ACLF， among whom 19 developed ACLF during follow-up. The patients with ACLF on admission had a significantly higher level of I-FABP than those without ACLF （Z=4.359， P<0.001）. The patients with new-onset ACLF had a significantly higher level of I-FABP than those without new-onset ACLF （Z=3.414， P<0.001）. The level of I-FABP increased with the increase in ACLF severity grade （H=17.385， P<0.001，P_trend<0.001）. The multivariate Cox regression analysis showed that I-FABP was independently associated with new-onset ACLF during follow-up （hazard ratio=2.138， 95% confidence interval ［CI］： 1.297 — 3.525， P=0.003）， and the tertile of I-FABP showed a good discriminatory ability （χ²=12.16， P<0.001）. The ROC curve showed that I-FABP had a good performance in predicting the development and progression of ACLF， with an area under the ROC curve of 0.854 （95%CI： 0.791 — 0.903） and 0.747 （95%CI： 0.661 — 0.820）， respectively， and an optimal cut-off value of 2.07 μg/L and 1.86 μg/L， respectively. Conclusion I-FABP can be used as a biomarker to predict the development and progression of ACLF， and it may help to identify high-risk patients and improve clinical management.
- Acute-On-Chronic Liver Failure /
- Fatty Acid-Binding Proteins /
- Biomarkers

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图 1 I-FABP与ACLF分级的关系

Figure 1. Relationship between I-FABP and ACLF grading

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图 2 ROC曲线分析I-FABP对ACLF的诊断效能

Figure 2. ROC curve analysis of I-FABP for diagnosing ACLF

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图 3 依据I-FABP三分位数分层的ACLF累积发生率

Figure 3. Cumulative incidence of ACLF stratified by I-FABP tertiles

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图 4 研究参数对新发ACLF的预测效能

Figure 4. Predictive efficacy of study parameters for ACLF

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表 1 研究人群基线特征

Table 1. Baseline characteristics of study population

指标	非ACLF组（n=125）	ACLF组（n=43）	统计值	P值
年龄（岁）	54（42～64）	55（48～67）	Z=1.795	0.073
男性［例（%）］	83（66.4）	32（74.4）	χ²=0.953	0.327
WBC（10⁹/L）	6.39（5.20～9.35）	8.13（6.61～10.12）	Z=3.140	0.002
CRP（mg/L）	13.9（8.3～40.6）	29.9（17.9～51.3）	Z=3.800	<0.001
Alb（g/L）	33（29～37）	28（27～31）	Z=5.054	<0.001
Cre（μmol/L）	85（75～106）	123（107～144）	Z=6.066	<0.001
TBil（μmol/L）	39.8（27.2～67.8）	171.5（116.7～233.1）	Z=8.915	<0.001
INR	1.30（1.04～1.74）	2.01（1.73～2.24）	Z=6.749	<0.001
MELD评分	15（11～21）	29（25～33）	Z=7.776	<0.001
I-FABP（μg/L）	1.51（0.87～2.55）	3.09（2.51～3.95）	Z=4.359	<0.001

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表 2 随访期间ACLF发展情况的临床资料比较

Table 2. Comparison of clinical data on the development of ACLF during the follow-up

指标	未发生ACLF组（n=106）	新发ACLF组（n=19）	统计值	P值
年龄（岁）	54（40～64）	53（47～62）	Z=0.678	0.498
男性［例（%）］	70（66.0）	13（68.4）	χ²=0.041	0.839
WBC（10⁹/L）	6.35（5.20～9.35）	6.69（5.45～10.22）	Z=0.589	0.556
CRP（mg/L）	13.2（7.7～40.7）	20.5（12.6～33.8）	Z=1.241	0.214
Alb（g/L）	34（30～37）	31（25～35）	Z=1.069	0.285
Cre（μmol/L）	84（75～105）	96（86～130）	Z=2.156	0.031
TBil（μmol/L）	37.4（26.0～67.8）	48.0（40.5～61.1）	Z=2.029	0.042
INR	1.26（1.02～1.61）	1.68（1.25～2.03）	Z=2.219	0.027
MELD评分	14（11～19）	21（18～23）	Z=3.867	<0.001
I-FABP（μg/L）	1.34（0.85～2.13）	2.69（1.91～3.14）	Z=3.414	<0.001

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表 3 多因素Cox回归分析随访期间发生ACLF的影响因素

Table 3. Multivariate Cox regression analyzed the factors of developing ACLF during follow-up

因素	β值	Wald	HR（95%CI）	P值
Cre	0.017	10.278	1.017（1.007～1.027）	0.001
I-FABP	0.760	8.880	2.138（1.297～3.525）	0.003
MELD评分	0.096	5.495	1.101（1.016～1.194）	0.019

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表 4 各指标对随访期间新发ACLF的预测性能

Table 4. Predictive performance of the study parameters on new-onset ACLF during follow-up

指标	AUC（95%CI）	Cut-off值	灵敏度（%）	特异度（%）	Z值	P值
Cre	0.656（0.565～0.738）	92.00	73.68	66.04	2.100	0.036
I-FABP	0.747（0.661～0.820）	1.86	78.95	62.26	4.275	<0.001
MELD评分	0.779（0.696～0.848）	16.00	89.47	61.32	6.617	<0.001
I-FABP+MELD评分	0.810（0.731～0.875）		73.68	80.19	5.955	<0.001

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