年龄和D-二聚体联合终末期肝病模型对HBV相关慢加急性肝衰竭患者预后的预测价值

董少雨; 孙长宇; 乔芳芳; 刘笑; 张建营

doi:10.3969/j.issn.1001-5256.2022.11.008

年龄和D-二聚体联合终末期肝病模型对HBV相关慢加急性肝衰竭患者预后的预测价值

DOI: 10.3969/j.issn.1001-5256.2022.11.008

1.
郑州大学第一附属医院感染科，郑州 450052
2.
郑州大学公共卫生学院，郑州 450001

基金项目:

国家科技重大专项子课题 (2018ZX10302205-004)

伦理学声明：本研究方案于2022年9月7日经由郑州大学第一附属医院伦理委员会审批，批号：2022-KY-0999-001。所纳入患者均签署知情同意书。

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：董少雨负责课题设计，资料分析，撰写论文；乔芳芳、刘笑负责收集数据和统计分析；张建营负责指导数据统计分析；孙长宇负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
孙长宇，changyu8188@163.com

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出版历程
- 收稿日期: 2022-04-21
- 录用日期: 2022-05-25
- 出版日期: 2022-11-20

Value of age and D-dimer combined with Model for End-Stage Liver Disease in predicting the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure

1.
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
2.
School of Public Health, Zhengzhou University, Zhengzhou 450001, China

Research funding:

Sub-project of the National Science and Technology Major Project (2018ZX10302205-004)

More Information

Corresponding author: SUN Changyu, changyu8188@163.com(ORCID: 0000-0001-9993-8098)

摘要

摘要: 目的探讨年龄和D-二聚体(D-D)联合终末期肝病模型(MELD)评分对HBV相关慢加急性肝衰竭(HBV-ACLF)患者预后的预测价值。方法选取2019年12月—2021年10月在郑州大学第一附属医院住院治疗的111例HBV-ACLF患者，根据确诊后90 d预后分为生存组(n=49)和死亡组(n=62)。收集患者的临床资料，包括年龄、性别、基础肝病、ALT、AST、TBil、Alb、D-D、PT、纤维蛋白原(FIB)、PTA、INR、SCr、血清钠(Na)，并计算MELD评分。采用免疫比浊法测定血浆D-D水平。计量资料两组间比较采用t检验或Mann-Whitney U检验；计数资料两组间比较采用χ²检验。采用二元Logistic回归分析影响患者预后的独立危险因素，受试者工作特征曲线(ROC曲线)用于评估预测变量的准确性。ROC曲线下面积(AUC)的比较采用Delong法。结果两组间年龄、TBil、D-D、PT、PTA、INR、SCr、Na、MELD评分比较差异均有统计学意义(P值均＜0.05)。进一步二元Logistic回归分析发现，年龄(OR=1.088，95%CI：1.001~1.183，P=0.047)、D-D(OR=1.521，95%CI：1.078~2.145，P=0.017)和MELD评分(OR=1.892，95%CI：1.408~2.543，P＜0.001)是影响HBV-ACLF患者预后的独立危险因素。年龄、MELD评分、D-D对HBV-ACLF预后预测的AUC分别为0.664、0.869、0.887，D-D联合年龄、年龄联合MELD评分、D-D联合MELD评分及三者联合的AUC分别为0.895、0.906、0.965、0.970，除D-D联合MELD评分外，三者联合的AUC较其他指标明显升高，差异均有统计学意义(P值均＜0.05)；三者联合的敏感度和特异度较高，分别是0.935、0.918。结论年龄、D-D、MELD评分是影响HBV-ACLF预后的独立危险因素，其中D-D和MELD评分对预后具有良好的预测价值，三者联合预测价值更高。
- 乙型肝炎病毒 /
- 慢加急性肝功能衰竭 /
- D-二聚体 /
- 预后
Abstract: Objective To investigate the value of age and D-dimer (D-D) combined with Model for End-Stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 111 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Zhengzhou University from December 2019 to October 2021 were enrolled, and according to their prognosis on day 90 after confirmed diagnosis, they were divided into survival group with 49 patients and death group with 62 patients. Related clinical data were collected, including age, sex, underlying liver diseases, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), Albumin (Alb), D-D, prothrombin time (PT), plasma fibrinogen (FIB), prothrombin activity (PTA), international normalized ratio (INR), serum creatinine (SCr), and serum sodium (Na), and MELD score was calculated. Immunoturbidimetric assay was used to measure the plasma level of D-D. The t-test or the Mann-Whitney U test was used for comparison of continuous data between the two groups, and the chi-square test was used for comparison of categorical data between the two groups; a binary Logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients, and the receiver operating characteristic (ROC) curve was used to predict the accuracy of variables. Results There were significant differences between the two groups in age, TBil, D-D, PT, PTA, INR, SCr, Na, and MELD score (all P < 0.05). The binary Logistic regression analysis showed that age (odds ratio [OR]=1.088, 95% confidence interval [CI]: 1.001-1.183, P=0.047), D-D (OR=1.521, 95%CI: 1.078-2.145, P=0.017), and MELD score (OR=1.892, 95%CI: 1.408-2.543, P < 0.001) were independent risk factors for the prognosis of HBV-ACLF patients. Age, MELD score and D-D had an area under the ROC curve (AUC) of 0.664, 0.869, and 0.887, respectively, in predicting the prognosis of HBV-ACLF, while D-D combined with age, age combined with MELD score, D-D combined with MELD score, and the combination of these three indicators had an AUC of 0.895, 0.906, 0.965, and 0.970, respectively. A combination of the three indices had a significantly increased AUC compared with other indices except D-D combined with MELD score. and the combination of these three indicators had relatively high sensitivity (0.935) and specificity (0.918). Conclusion Age, D-D, and MRLD score are independent risk factors for the prognosis of HBV-ACLF, among which D-D and MELD score have a good value in predicting prognosis, and the combination of these three indicators has a significantly better predictive value.
- Hepatitis B Virus /
- Acute-On-Chronic Liver Failure /
- D-Dimer /
- Prognosis

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图 1 年龄、D-D及MELD评分对HBV - ACLF预后预测的ROC曲线

Figure 1. ROC curve of D-D, age and MELD score in predicting the prognosis of HBV-ACLF

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表 1 HBV-ACLF患者入院情况

Table 1. Admission status of HBV-ACLF patients

指标	生存组(n=49)	死亡组(n=62)	统计值	P值
年龄(岁)	43.33±9.69	48.78±12.28	t=2.549	0.012
男/女(例)	38/11	46/16	χ²=0.168	0.682
慢性乙型肝炎/肝硬化(例)	12/37	13/49	χ²=0.195	0.659
ALT(U/L)	252.0(72.0~652.0)	186.0(46.0~593.5)	Z=-0.502	0.616
AST(U/L)	185.0(91.5~469.5)	172.5(73.5~422.5)	Z=-0.499	0.618
Alb(g/L)	30.8(28.3~38.2)	29.3(27.3~32.1)	Z=-1.375	0.169
TBil(μmol/L)	247.68±100.53	330.01±118.67	t=3.879	＜0.001
D-D(mg/L)	0.42(0.31~1.34)	1.89(1.50~3.59)	Z=-6.987	＜0.001
PT(s)	24.40(22.05~27.70)	27.50(24.05~31.95)	Z=-3.059	0.002
FIB(g/L)	1.11(0.95~1.44)	1.16(0.90~1.39)	Z=-0.358	0.720
PTA(%)	32.0(27.0~36.0)	29.0(23.5~33.8)	Z=-2.585	0.010
INR	2.20(2.00~2.54)	2.44(2.16~2.95)	Z=-3.035	0.002
SCr(μmol/L)	51.8(42.0~67.5)	60.0(50.0~80.0)	Z=-3.849	＜0.001
Na(mmol/L)	138(135~139)	135(131~139)	Z=-3.017	0.003
MELD评分	13.82(11.89~16.87)	17.46(14.84~21.35)	Z=-6.663	＜0.001

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表 2 预后危险因素的单因素Logistic回归分析

Table 2. Univariate Logistic regression analysis of prognostic risk factors

因素	β值	Wald值	OR	95%CI	P值
性别	-0.184	0.167	0.832	0.345~2.006	0.682
年龄	0.044	5.925	1.045	1.009~1.083	0.015
慢性乙型肝炎/肝硬化	0.201	0.194	1.222	0.500~2.986	0.695
D-D	2.093	22.715	8.113	3.430~19.189	＜0.001
FIB	0.132	0.264	1.142	0.689~1.890	0.607
PT	0.980	6.587	1.103	1.023~1.189	0.010
PTA	-0.076	6.774	0.927	0.876~0.981	0.009
INR	1.117	6.807	3.055	1.320~7.068	0.009
ALT	0.000	0.009	1.000	0.999~1.001	0.924
AST	0.000	0.134	1.000	0.999~1.001	0.714
Alb	-0.021	0.264	0.979	0.904~1.061	0.607
TBil	0.007	12.109	1.007	1.003~1.011	0.001
SCr	0.010	0.989	1.010	0.991~1.029	0.320
Na	-0.125	7.410	0.882	0.806~0.966	0.006
MELD评分	0.489	25.266	1.646	1.355~1.999	＜0.001

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表 3 年龄、D-D及MELD评分对HBV-ACLF预后的预测价值

Table 3. The prognostic value of age, D-D and MELD score for HBV-ACLF

指标	AUC	约登指数	临界值	敏感度(%)	特异度(%)	P值	95%CI
年龄	0.664	0.209	44.5	59.7	61.2	0.003	0.563~0.764
MELD评分	0.869	0.611	16.792	77.4	83.7	＜0.001	0.802~0.937
D-D	0.887	0.618	1.215	90.3	71.4	＜0.001	0.826~0.948
D-D联合年龄	0.895	0.685	0.506	83.9	81.6	＜0.001	0.836~0.953
年龄联合MELD评分	0.906	0.671	0.485	85.5	81.6	＜0.001	0.851~0.961
D-D联合MELD评分	0.965	0.813	0.427	93.5	87.8	＜0.001	0.933~0.997
D-D、年龄联合MELD评分	0.970	0.854	0.494	93.5	91.8	＜0.001	0.941~0.999

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