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苄氯素1、黏蛋白结构域3、白细胞介素34在急性肝衰竭中的表达及对患者疾病转归的预测价值
作者:王刚1  巩博1  余治国1  苏芮1  周彬1  周春芳2  陆卫华1 
单位:1. 中部战区总医院 急诊医学科 湖北 武汉 430070 2. 湖北医药学院附属太和医院 肝病科 湖北 十堰 442000 
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出版年,卷(期):页码:2024,16(3):45-51
摘要:

 摘要:目的 探讨苄氯素1(Beclin1)、黏蛋白结构域3(mucin domain 3,TIM-3)、白

细胞介素-34(interleukin 34,IL-34)在急性肝衰竭患者中的表达及对疾病转归的预测价
值。方法 选取2020年1月至2022年1月于中部战区总医院就诊的80例急性肝衰竭患者为
急性肝衰竭组,以同期于本院体检的80例健康人群作为健康组。通过酶联免疫吸附试
验法测定Beclin1、IL-34表达水平,通过流式细胞术测定TIM-3表达水平,比较两组患者
外周血Beclin1、TIM-3、IL-34表达水平差异。急性肝衰竭患者均接受保肝、人工肝或肝
移植治疗,根据治疗后疾病转归分为存活组(56例)和死亡组(24例),比较两组患者
Beclin1、TIM-3、IL-34的表达水平。采用Pearson相关系数分析Beclin1、TIM-3、IL-34与肝功能
指标的相关性,采用多因素Logistic回归分析影响急性肝衰竭患者病情转归的危险因素,
采用受试者工作特征(receiver operator characteristic,ROC)曲线分析Beclin1、TIM-3、
IL-34对急性肝衰竭患者病情转归的预测效能。结果 与健康组比较,急性肝衰竭组患者
外周血Beclin1 [(13.42 ± 2.11)μg/L 比(8.10 ± 1.12)μg/L]、TIM-3 [(44.53 ± 3.29)%
比(20.19 ± 2.31)%]、IL-34 [(15.53 ± 2.05)ng/L 比(9.73 ± 1.13)ng/L] 表达水平均
升高(P < 0.05)。Pearson相关性分析显示,急性肝衰竭患者外周血Beclin1、TIM-3、
IL-34水平与肝功能指标 [总胆红素(total bilirubin,TBil)、丙氨酸氨基转移酶(alanine
aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)]
均呈正相关(P均< 0.05)。与存活组患者比较,死亡组患者外周血Beclin1 [(15.64 ±
2.13)μg/L 比(10.02 ± 1.54)μg/L]、TIM-3 [(51.32 ± 6.75)% 比(35.64 ± 3.41)%]、
IL-34 [(19.08 ± 2.43)ng/L 比(11.12 ± 1.32)ng/L] 表达水平均升高(P < 0.05)。多
因素Logistic回归分析表明Beclin1(OR = 4.536,95%CI:3.442~8.904,P < 0.001)、
TIM-3(OR = 2.342,95%CI:1.023~6.757,P < 0.001)、IL-34(OR = 5.642,95%CI:
3.452~9.089,P < 0.001)升高均是影响急性肝衰竭患者疾病转归的独立危险因素。ROC
曲线分析表明,Beclin1、TIM-3、IL-34单项的曲线下面积分别为0.897、0.839、0.800,
三项联合预测急性肝衰竭转归的曲线下面积为0.934,显著高于各指标单项预测(Z =
2.272,P = 0.011;Z = 2.246,P = 0.014;Z = 3.980,P < 0.001)。结论 Beclin1、TIM-3、
IL-34高表达于急性肝衰竭患者中,且与疾病转归相关,死亡患者外周血Beclin1、TIM-3、
IL-34水平升高加剧,临床可根据三者在患者外周血中的表达水平早期预测急性肝衰竭转
归,以改善患者预后。

 Abstract: Objective To investigate the expression of Beclin1, mucin domain 3 (TIM-3) and

interleukin-34 (IL-34) in patients with acute liver failure and their predictive value for disease
outcomes. Methods Total of 80 patients with acute liver failure who received medical treatment in
General Hospital of the Central Theater Command from January 2020 to January 2022 were selected
as acute liver failure group, and 80 healthy individuals who underwent physical examinations in our
hospital during the same period were selected as healthy group. The expression levels of Beclin1
and IL-34 were measured by enzyme-linked immunosorbent assay, and TIM-3 was measured by
flow cytometry. All patients with acute liver failure were treated with liver protection, artificial liver
or liver transplantation. They were divided into survival group (56 cases) and death group (24 cases)
according to the outcome of the disease after treatment. The expression levels of Beclin1, TIM-
3 and IL-34 of patients in two groups were compared. Pearson correlation coefficient was used to
analyze the correlation between Beclin1, TIM-3, IL-34 and liver function indicators. Multivariate
Logistic regression was used to analyze the risk factors affecting the prognosis of acute liver failure
patients. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of
Beclin1, TIM-3, IL-34 on the prognosis of patients with acute liver failure. Results Compared with
those of healthy group, Beclin1 [(13.42 ± 2.11) μg/L vs. (8.10 ± 1.12) μg/L], TIM-3 [(44.53 ± 3.29)%
vs. (20.19 ± 2.31)%] and IL-34 [(15.53 ± 2.05) ng/L vs. (9.73 ± 1.13) ng/L] expression levels of
patients in acute liver failure group increased significantly (all P < 0.05). Pearson correlation
analysis showed that the levels of Beclin1, TIM-3 and IL-34 in peripheral blood of patients with
acute liver failure were positively correlated with liver function indicators [total bilirubin (TBil),
alanine aminotransferase (ALT), aspartate aminotransferase (AST)] (all P < 0.05). Compared with
those of survival group, Beclin1 [(15.64 ± 2.13) μg/L vs. (10.02 ± 1.54) μg/L], TIM-3 [(51.32 ±
6.75)% vs. (35.64 ± 3.41)%] and IL-34 [(19.08 ± 2.43) ng/L vs. (11.12 ± 1.32) ng/L] expression
levels of patients in death group increased significantly (all P < 0.05). Multivariate Logistic
regression analysis showed that elevated Beclin1 (OR = 4.536, 95%CI: 3.442~8.904, P < 0.001), TIM-3
(OR = 2.342, 95%CI: 1.023~6.757, P < 0.001) and IL-34 (OR = 5.642, 95%CI: 3.452~9.089,
P < 0.001) were independent risk factors affecting the outcome of patients with acute liver failure.
ROC curve showed that the areas under the curve of Beclin1, TIM-3 and IL-34 were 0.897, 0.839
and 0.800, respectively. The area under the curve of Beclin1 + TIM-3 + IL-34 was 0.934, which was
significantly higher than those of the individual indicators (Z = 2.272, P = 0.011; Z = 2.246, P = 0.014;
Z = 3.980, P < 0.001). Conclusions Beclin1, TIM-3 and IL-34 were highly expressed in patients
with acute liver failure and were associated with the outcomes. The increase of Beclin1, TIM-3 and
IL-34 in peripheral blood of patients in death group was exacerbated. Clinically, the disease outcome
could be predicted early according to the expression level of the three indicators in the peripheral
blood of patients to improve the outcome.
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