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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参考文献(24)

[1]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007. 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.
[2]	BAJA JS, O'LEARY JG, LAI JC, et al. Acute-on-chronic liver failure clinical guidelines[J]. Am J Gastroenterol, 2022, 117(2): 225-252. DOI: 10.14309/ajg.0000000000001595.
[3]	SHANG DB, XIANG XG. Advances in the pathogenesis and treatment of acute-on-chronic liver failure[J]. J Clin Hepatol, 2021, 37(4): 765-769. DOI: 10.3969/j.issn.1001-5256.2021.04.005. 尚大宝, 项晓刚. 慢加急性肝衰竭的发病机制和治疗进展[J]. 临床肝胆病杂志, 2021, 37(4): 765-769. DOI: 10.3969/j.issn.1001-5256.2021.04.005.
[4]	ZHANG TY, YU YP, XIA Q, et al. Research progress in liver transnlantation for acute-on-chronic liver failure[J]. Shanghai Jiaotong Univ (Medical Science), 2021, 41(2): 257-261. DOI: 10.3969/j.issn.1674-8115.2021.02.021. 张天翼, 于也萍, 夏强, 等. 肝移植治疗慢加急性肝衰竭研究进展[J]. 上海交通大学学报(医学版), 2021, 41(2): 257-261. DOI: 10.3969/j.issn.1674-8115.2021.02.021.
[5]	FAN Q, LI Z. Liver transplantation for acute-on-chronic liver failure[J]. Ogran Transplant, 2022, 13(3): 333-337. DOI: 10.3969/j.issn.1674-7445.2022.03.008. 范祺, 李照. 慢加急性肝衰竭的肝移植治疗[J]. 器官移植, 2022, 13(3): 333-337. DOI: 10.3969/j.issn.1674-7445.2022.03.008.
[6]	YUE HW, WANG YY. Change rule of blood coagulation, fibrinolysis and anti-coagulation indexes during the progress of chronic hepatitis B[J]. Lab Med Clin, 2020, 17(6): 755-757. DOI: 10.3969/j.issn.1672-9455.2020.06.010. 乐华文, 王依屹. 凝血、纤溶和抗凝指标在慢性乙型肝炎病情进展中的变化规律[J]. 检验医学与临床, 2020, 17(6): 755-757. DOI: 10.3969/j.issn.1672-9455.2020.06.010.
[7]	YU B, PENG FE. The value of coagulation of the four combined with D-dimer detection in the severity of hepatitis B patients[J]. Chin J Thromb Hemostasis, 2021, 27(3): 431-432. 于波, 彭粉娥. 凝血四项联合D二聚体水平检测在乙型肝炎患者严重程度的价值探讨[J]. 血栓与止血学, 2021, 27(3): 431-432.
[8]	QI T, ZHU C, LU G, et al. Elevated D-dimer is associated with increased 28-day mortality in acute-on-chronic liver failure in China: a retrospective study[J]. BMC Gastroenterol, 2019, 19(1): 20. DOI: 10.1186/s12876-019-0941-0.
[9]	Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
[10]	Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006. 中华医学会肝病学分会. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
[11]	XU Y, HUANG XP, CHEN L, et al. Role of coagulation abnormalities in thrombosis in patients with hepatitis B virus -associated acute -on -chronic liver failure[J]. J Clin Hepatol, 2021, 37(3): 560-564. DOI: 10.3969/j.issn.1001-5256.2021.03.012. 徐英, 黄小平, 陈丽, 等. 凝血异常在HBV相关慢加急性肝衰竭患者血栓形成中的作用[J]. 临床肝胆病杂志, 2021, 37(3): 560-564. DOI: 10.3969/j.issn.1001-5256.2021.03.012.
[12]	ZHU LD, CAI LP, CHEN AZ, et al. Clinical significance of D-dimer and other fibrinolytic markers in chronic hepatitis[J]. Chin Health Stand Manage, 2021, 12(19): 94-97. DOI: 10.3969/j.issn.1674-9316.2021.19.031. 朱李登, 蔡丽平, 陈爱灼, 等. D二聚体及其他纤溶指标在慢性肝炎的临床意义[J]. 中国卫生标准管理, 2021, 12(19): 94-97. DOI: 10.3969/j.issn.1674-9316.2021.19.031.
[13]	XU ZJ. Significance of FDP, antithrombin-Ⅲ and D-dimer levels in patients with chronic liver disease[J]. Contemp Med, 2021, 27(22): 9-10. DOI: 10.3969/j.issn.1009-4393.2021.22.004. 许志坚. 慢性肝病患者FDP和抗凝血酶-Ⅲ以及D-二聚体水平检测的意义[J]. 当代医学, 2021, 27(22): 9-10. DOI: 10.3969/j.issn.1009-4393.2021.22.004.
[14]	LONG D, YU L, WU XL. A study of dynamic changes of plasma D- dimer and cytokine of patients with systemic inflammatory response syndrome[J]. Chongqing Med, 2012, 41(8): 738-740, 743. DOI: 10.3969/j.issn.1671-8348.2012.08.004. 龙鼎, 喻莉, 武晓灵. 系统性炎症反应综合征患者血浆D-二聚体与细胞因子动态变化的研究[J]. 重庆医学, 2012, 41(8): 738-740, 743. DOI: 10.3969/j.issn.1671-8348.2012.08.004.
[15]	HERNAEZ R, SOLÀ E, MOREAU R, et al. Acute-on-chronic liver failure: an update[J]. Gut, 2017, 66(3): 541-553. DOI: 10.1136/gutjnl-2016-312670.
[16]	JIANG W, ZHENG ZM, LI J. Application of rapid determination of plasma D-dimer in liver disease changes and correlation of coagulation, fibrinolysis, and anticoagulation indexes in patients with chronic liver failure[J]. Lab Med Clin, 2019, 16(22): 3340-3343. DOI: 10.3969/j.issn.1672-9455.2019.22.032. 蒋雯, 郑泽美, 李军. 凝血、纤溶与抗凝指标在慢性肝衰竭患者中的变化及相关性[J]. 检验医学与临床, 2019, 16(22): 3340-3343. DOI: 10.3969/j.issn.1672-9455.2019.22.032.
[17]	YU L, LONG D, WU XL, et al. The expression of uPA and uPAR in patients with systemic inflammatory response syndrome[J]. Chin J Emerg Med, 2011, 20(10): 1079-1083. DOI: 10.3760/cma.j.issn.1671-0282.2011.10.018. 喻莉, 龙鼎, 武晓灵, 等. 全身炎症反应综合征中血浆尿激酶型纤溶酶原激活物及其受体的表达[J]. 中华急诊医学杂志, 2011, 20(10): 1079-1083. DOI: 10.3760/cma.j.issn.1671-0282.2011.10.018.
[18]	LIU YG, LI CS. Significance of lactic acid and D-dimer in patients with systemic inflammatory response syndrome[J]. Chin J Crit Care Med, 2003, 23(12): 851-852. DOI: 10.3969/j.issn.1002-1949.2003.12.012. 刘禹赓, 李春盛. 血乳酸和D-二聚体测定在全身炎症反应综合征中的意义[J]. 中国急救医学, 2003, 23(12): 851-852. DOI: 10.3969/j.issn.1002-1949.2003.12.012.
[19]	ZHANG WJ, ZHAO LJ, WU JZ. Value of MELD、AARC、COSSH ccoring systems in evaluating the 90-day prognosis of hepatitis B virus-related acute-on-chronic liver failure[J]. J Clin Hepatol, 2020, 36(4): 813-817. DOI: 10.3969/j.issn.1001-5256.2020.04.021. 张文佳, 赵丽娟, 吴基洲. MELD、AARC、COSSH评分系统对乙型肝炎相关慢加急性肝衰竭90天预后的评估价值[J]. 临床肝胆病杂志, 2020, 36(4): 813-817. DOI: 10.3969/j.issn.1001-5256.2020.04.021.
[20]	YANG S, LI XT, YANG L, et al. Research progress on prognostic models of acute-on-chronic liver failure associated with hepatitis B[J]. Int J Epidemiol Infect Dis, 2022, 49(1): 61-65. DOI: 10.3760/cma.j.cn331340-20210415-00076. 杨烁, 李新婷, 杨兰, 等. 乙型肝炎相关慢加急性肝衰竭的预后模型[J]. 国际流行病学传染病学杂志, 2022, 49(1): 61-65. DOI: 10.3760/cma.j.cn331340-20210415-00076.
[21]	MING F, ZHANG Y, LI ZM, et al. Value of IL-33 and sST2 combined with MELD score in predicting short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure[J]. Jiangsu Med J, 2022, 48(2): 186-190. DOI: 10.19460/j.cnki.0253-3685.2022.02.022.
[22]	LIN XF, LI LF, YU XY, et al. MELD-based models predict the prognosis of patients with acute-on-chronic hepatitis B liver failure[J/CD]. Chin J Clinician(Electronic Edition), 2012, 6(19): 5853-5857. DOI: 10.3877/cma.j.issn.1674-0785.2012.19.021. 林贤丰, 李凌菲, 俞燮琰, 等. MELD相关评分体系对乙型肝炎相关慢加急性肝衰竭患者预后的预测价值[J/CD]. 中华临床医师杂志(电子版), 2012, 6(19): 5853-5857. DOI: 10.3877/cma.j.issn.1674-0785.2012.19.021.
[23]	TIAN XL, PENG Y, WU SL, et al. Liver failure staging and MELD predicted the short term prognosis of HBV-acute-on-chronic liver failure[J]. Chongqing Med, 2017, 46(8): 1079-1081. DOI: 10.3969/j.issn.1671-8348.2017.08.023. 田小利, 彭颖, 吴松林, 等. 肝衰竭分期联合MELD评分对肝衰竭短期预后判断的研究[J]. 重庆医学, 2017, 46(8): 1079-1081. DOI: 10.3969/j.issn.1671-8348.2017.08.023.
[24]	ZHAO J, LI L, LI XH, et al. Value of a new predictive model in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure[J]. Chin Critical Care Med, 2020, 32(8): 988-993. DOI: 10.3760/cma.j.cn121430-20200102-00075. 赵洁, 李力, 李秀惠, 等. 乙型肝炎病毒相关慢加急性肝衰竭患者短期预后模型的建立及预测价值研究[J]. 中华危重病急救医学, 2020, 32(8): 988-993. DOI: 10.3760/cma.j.cn121430-20200102-00075.