血清簇集蛋白、1-磷酸鞘氨醇水平对脓毒症急性肝损伤患者的预后价值

徐大洲; 张树贤; 王坤; 左晨艳; 曾毅; 袁青文; 张志梅

doi:10.3969/j.issn.1001-5256.2023.12.018

血清簇集蛋白、1-磷酸鞘氨醇水平对脓毒症急性肝损伤患者的预后价值

DOI: 10.3969/j.issn.1001-5256.2023.12.018

徐州医科大学附属连云港医院消化内科，江苏连云港 222000

基金项目:

江苏省连云港市卫生健康科研项目 (ZD1903)

伦理学声明：本研究方案于2019年2月10日经由徐州医科大学附属连云港医院伦理委员会审批，批号：2019-0213，所纳入患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：徐大洲、张树贤负责课题设计，资料分析，撰写论文；王坤、左晨艳参与收集数据，修改论文；曾毅、袁青文、张志梅负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
张志梅， 1365360153@qq.com （ORCID： 0009-0002-8793-1432）

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出版历程
- 收稿日期: 2023-07-21
- 录用日期: 2023-08-23
- 出版日期: 2023-12-12

Value of the serum levels of Clusterin and sphingosine 1-phosphate in assessing the prognosis of sepsis patients with acute liver injury

Department of Gastroenterology，Lianyungang Hospital，Xuzhou Medical University，Lianyungang，Jiangsu 222000，China

Research funding:

Health Research Project of Lianyungang city in Jiangsu Province (ZD1903)

More Information

Corresponding author: ZHANG Zhimei， 1365360153@qq.com （ORCID： 0009-0002-8793-1432）

摘要

摘要: 目的探讨血清簇集蛋白（Clusterin）、1-磷酸鞘氨醇（S1P）水平对脓毒症急性肝损伤患者预后的评估价值。方法选择2019年3月—2022年5月徐州医科大学附属连云港医院收治的脓毒症急性肝损伤患者127例，根据患者治疗28 d预后情况分为死亡组35例、存活组92例。计量资料两组间比较采用成组t检验，计数资料两组间比较采用χ²检验，对可能影响患者预后的各因素进行单因素及多因素Logistic回归分析，相关性分析采用Pearson相关性分析，采用受试者工作特征曲线分析血清Clusterin、S1P对患者预后评估价值。结果两组患者肝损伤程度、急性生理学与慢性健康状况评分Ⅱ（APACHE Ⅱ）、序贯器官衰竭评分（SOFA）、合并急性肾损伤、凝血酶原时间（PT）、国际标准化比值（INR）、Child-Pugh肝功能分级以及C反应蛋白比较差异均有统计学意义（P值均<0.05）。死亡组患者血清Clusterin、S1P水平均显著低于存活组（t值分别11.094、10.390，P值均<0.05）。重度肝损伤患者血清Clusterin、S1P水平显著低于轻、中度肝损伤患者（t值分别为9.825、11.418，P值均<0.05）。多因素回归分析显示，肝损伤程度（OR=1.260，95%CI：1.081～1.468）、APACHE Ⅱ评分（OR=1.031，95%CI：1.019～1.044）、SOFA评分（OR=1.066，95%CI：1.039～1.094）、Clusterin（OR=0.899，95%CI：0.859～0.940）和S1P（OR=0.824，95%CI：0.749～0.908）为影响脓毒症患者预后的独立危险因素（P值均<0.05）。ROC曲线分析结果显示，血清Clusterin、S1P与二者联合对患者预后评估价值的曲线下面积分别为0.864、0.861、0.949。脓毒症急性肝损伤患者血清Clusterin、S1P与ALT、TBil、PT、INR均呈显著负相关关系（P值均<0.05）。结论与存活组相比，脓毒症急性肝损伤死亡患者血清Clusterin以及S1P显著降低，且Clusterin以及S1P水平与患者肝损伤程度密切相关，二者联合对脓毒症急性肝损伤患者预后具有着较好的预测价值，有望成为脓毒症急性肝损患者预后预测的潜在标志物。
- 脓毒症 /
- 急性肝损伤 /
- 聚集素 /
- 1-磷酸鞘氨醇 /
- 预后
Abstract: Objective To investigate the value of the serum levels of Clusterin and sphingosine 1-phosphate （S1P） in assessing the prognosis of sepsis patients with acute liver injury. Methods A total of 127 sepsis patients with acute liver injury who were admitted to Lianyungang Hospital， Xuzhou Medical University， from March 2019 to May 2022 were enrolled， and according to their prognosis after 28 days of treatment， they were divided into death group with 35 patients and survival group with 92 patients. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. A pearson correlation analysis was used to investigate the correlation. The prognostic value of serum Clusterin and S1P was analyzed by receiver operating characteristic curve. Results There were significant differences between the two groups in the degree of liver injury， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHEⅡ） score， Sequential Organ Failure Assessment （SOFA） score， the presence or absence of acute kidney injury， prothrombin time （PT）， international normalized ratio （INR）， Child-Pugh class， and C-reactive protein （all P<0.05）. The death group had significantly lower serum levels of Clusterin and S1P than the survival group （t=11.094 and 10.390， both P<0.05）. The patients with severe liver injury had significantly lower serum levels of Clusterin and S1P than those with mild or moderate liver injury （t=9.825 and 11.418， both P<0.05）. The multivariate regression analysis showed that the degree of liver injury （odds ratio ［OR］=1.260， 95% confidence interval ［CI］： 1.081 — 1.468， P<0.05）， APACHEII score （OR=1.031， 95%CI： 1.019 — 1.044， P<0.05）， SOFA score （OR=1.066， 95%CI： 1.039 — 1.094， P<0.05）， Clusterin （OR=0.899， 95%CI： 0.859 — 0.940， P<0.05）， and S1P （OR=0.824， 95%CI： 0.749 — 0.908， P<0.05） were independent risk factors for the prognosis of patients with sepsis. The ROC curve analysis showed that serum Clusterin and S1P used alone or in combination had an area under the ROC curve of 0.864， 0.861， and 0.949， respectively. Serum Clusterin and S1P were significantly negatively correlated with alanine aminotransferase， total bilirubin， PT， and INR in sepsis patients with acute liver injury （all P<0.05）. Conclusion The sepsis patients with acute liver injury who died had significant reductions in serum Clusterin and S1P compared with those who survived， and the levels of Clusterin and S1P are closely associated with the degree of liver injury. The combination of Clusterin and S1P has a good value in predicting the prognosis of sepsis patients with acute liver injury and is expected to become a potential marker for predicting the prognosis of sepsis patients with acute liver injury.
- Sepsis /
- Acute Liver Injury /
- Clusterin /
- Sphingosine-1-Phosphate /
- Prognosis

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图 1 血清Clusterin、S1P对患者预后评估ROC曲线

Figure 1. The ROC curve of serum Clusterin and S1P was used to evaluate the prognosis of patients

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表 1 两组患者临床资料比较

Table 1. Comparison of clinical data between the two groups

指标	死亡组（n=35）	存活组（n=92）	统计值	P值
性别（例）			χ²=0.045	0.831
男	19	48
女	16	44
年龄（岁）	57.28±10.21	58.33±10.93	t=0.492	0.623
HR（次/min）	123.95±17.33	121.64±15.62	t=0.722	0.471
MAP（mmHg）	60.49±9.85	61.11±10.21	t=0.309	0.758
感染部位（例）			χ²=1.511	0.680
肺及胸腔	6	19
腹腔	7	22
泌尿系	9	27
其他	13	24
肝损伤程度（例）			χ²=11.825	0.001
轻度、中度	14	67
重度	21	25
APACHE Ⅱ评分	24.59±6.22	17.32±5.25	t=6.189	<0.001
SOFA评分	15.28±3.12	12.10±2.11	t=6.598	<0.001
机械通气（例）			χ²=0.233	0.630
是	13	30
否	22	62
合并凝血功能障碍（例）			χ²=0.378	0.539
是	9	19
否	26	73
合并急性肾损伤（例）			χ²=7.995	0.005
是	15	17
否	20	75
氧合指数（mmHg）	126.92±25.20	128.52±21.50	t=0.357	0.722
PT（s）	16.94±2.41	15.38±2.16	t=3.369	0.001
INR	1.95±0.31	1.64±0.26	t=5.686	<0.001
Child-Pugh分级（例）			χ²=-2.485	0.013
A级	3	24
B级	17	45
C级	15	23
CRP（mg/L）	22.39±5.17	19.38±4.22	t=3.369	0.001

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表 2 两组患者血清Clusterin、S1P水平比较

Table 2. Comparison of serum Clusterin and S1P levels between two groups

组别	例数	Clusterin（μg/mL）	S1P（ng/mL）
死亡组	35	34.38±10.21	109.38±26.49
存活组	92	92.74±30.41	197.43±47.32
t值		11.094	10.390
P值		<0.001	<0.001

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表 3 不同肝损伤程度患者血清Clusterin、S1P水平比较

Table 3. Comparison of blood Clusterin and S1P levels in patients with different degrees of liver injury

组别	例数	Clusterin（μg/mL）	S1P（ng/mL）
轻、中度	81	96.27±35.62	205.73±47.39
重度	46	42.59±13.31	115.48±33.15
t值		9.825	11.418
P值		<0.001	<0.001

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表 4 影响患者预后的多因素分析

Table 4. Multivariate analysis affecting prognosis of patients

指标	B值	SE	χ²值	P值	OR	95%CI
肝损伤程度（轻、中度=0，重度=1）	0.231	0.078	8.771	0.003	1.260	1.081～1.468
APACHE Ⅱ评分	0.031	0.006	26.694	<0.001	1.031	1.019～1.044
SOFA评分	0.064	0.013	24.237	<0.001	1.066	1.039～1.094
Clusterin	-0.107	0.023	21.643	<0.001	0.899	0.859～0.940
S1P	-0.193	0.049	15.514	<0.001	0.824	0.749～0.908

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表 5 ROC曲线分析血清Clusterin、S1P对患者预后评估价值

Table 5. ROC curve was used to analyze the prognostic value of serum Clusterin and S1P

指标	曲线下面积	最佳截断值	敏感度（%）	特异度（%）	P值	95%CI
Clusterin	0.864	54.015 μg/mL	84.80	88.60	<0.001	0.781～0.947
S1P	0.861	152.931 ng/mL	81.50	85.70	<0.001	0.784～0.938
联合	0.949	-	87.00	91.40	<0.001	0.915～0.983

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表 6 患者血清Clusterin、S1P与ALT、TBil、PT、INR相关性分析

Table 6. Correlation analysis of serum Clusterin， S1P， ALT， TBil， PT and INR

指标	ALT	TBil	PT	INR
Clusterin
r值	-0.426	-0.365	-0.316	-0.297
P值	<0.001	<0.001	<0.001	<0.001
S1P
r值	-0.397	-0.411	-0.325	-0.305
P值	<0.001	<0.001	<0.001	<0.001

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