慢加急性肝衰竭急性静脉曲张出血的危险因素及预后分析

刘婉姝; 申力军; 翟庆慧; 辛绍杰; 游绍莉

doi:10.3969/j.issn.1001-5256.2022.11.018

慢加急性肝衰竭急性静脉曲张出血的危险因素及预后分析

DOI: 10.3969/j.issn.1001-5256.2022.11.018

解放军总医院第五医学中心肝病医学部肝病科，北京 100039

基金项目:

国家“十三五”科技重大专项 (2017ZX10203201-004)

伦理学声明：本研究方案经过原解放军第302医院临床研究伦理委员会批准，批号：2013005D、2019085D。

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：刘婉姝、申力军负责课题设计，资料分析，撰写论文；翟庆慧参与收集及分析数据；辛绍杰、游绍莉负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
游绍莉，youshaoli1972@163.com

作者说明：刘婉姝和申力军对本文贡献等同，同为第一作者

计量
- 文章访问数: 410
- HTML全文浏览量: 71
- PDF下载量: 38
- 被引次数: 0
出版历程
- 收稿日期: 2022-05-05
- 录用日期: 2022-06-20
- 出版日期: 2022-11-20

Risk factors for acute variceal bleeding in acute-on-chronic liver failure and its influence on prognosis

Department of Liver Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China

Research funding:

The 13th Five-Year National Science and Technology Major Project for Infectious Diseases (2017ZX10203201-004)

More Information

Corresponding author: YOU Shaoli, youshaoli1972@163.com(ORCID: 0000-0001-8689-8509)

摘要

摘要: 目的探讨慢加急性肝衰竭(ACLF)急性静脉曲张出血(AVB)的危险因素及对预后的影响。方法对解放军总医院第五医学中心2009年—2015年收治ACLF患者1409例随访6个月，根据是否出现AVB分为AVB组(n=167)和非AVB组(n=1242)。计量资料符合正态分布两组间比较使用Student t检验；不符合正态分布资料两组间比较采用Mann-Whitney U检验。Kaplan-Meier法绘制生存曲线，对随访过程中组间病死率及进展进行Log-rank检验。采用二元Logistic回归分析AVB发生的危险因素。结果 1409例患者发生AVB 167例，占11.85%。AVB及非AVB患者30 d存活率分别为43.42%、67.79%(χ²=33.558，P＜0.001)；两组患者180 d存活率分别为18.91%、53.97%(χ²=76.881，P＜0.001)。Log-rank检验显示AVB与非AVB患者30 d生存率、180 d生存率差异均有统计学意义(χ²值分别为40.950、89.320，P值均＜0.05)。Logistic回归分析AVB发生的危险因素，胸腔积液(OR=1.522，95%CI: 1.071 ~2.162，P=0.019)、急性肾损伤(OR=2.201，95%CI: 1.415~3.426，P＜0.001)、ACLF分型(OR=2.491，95%CI: 1.489~4.168，P=0.001)、ACLF分期(OR=2.403，95%CI: 1.687~3.421，P＜0.001)及尿素(OR=2.567，95%CI：1.570~4.196，P＜0.001)与ACLF患者AVB的发生独立相关。结论 AVB是影响ACLF近期生存的重要因素，胸腔积液、急性肾损伤、ACLF分型BC型、ACLF晚期以及尿素是AVB发生的独立危险因素。
- 慢加急性肝功能衰竭 /
- 静脉曲张 /
- 危险因素 /
- 预后
Abstract: Objective To investigate the risk factors for acute variceal bleeding (AVB) in acute-on-chronic liver failure (ACLF) and its influence on prognosis. Methods A total of 1409 ACLF patients who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from 2009 to 2015 were followed up for 6 months, and according to the presence or absence of AVB, they were divided into AVB group and non-AVB group. The Student's t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier curves were plotted and the Log-rank test was performed to analyze mortality rate and progression during follow-up, and a binary Logistic regression analysis was used to investigate the risk factors for AVB. Results Among these 1409 patients, 167 (11.85%) experienced AVB. The 30-day survival rate was 43.42% in the AVB group and 67.79% in the non-AVB group (χ²=33.558, P < 0.001), and the 180-day survival rate was 18.91% in the AVB group and 53.97% in the non-AVB group (χ²=76.881, P < 0.001). The Log-rank test showed significant differences in 30- and 180-day survival rates between the AVB group and the non-AVB group (χ²=40.950 and 89.320, both P < 0.05). The Logistic regression analysis showed that pleural effusion (odds ratio [OR]=1.522, 95% confidence interval [CI]: 1.071-2.162, P=0.019), acute kidney injury (AKI) (OR=2.201, 95%CI: 1.415-3.426, P < 0.001), ABC subtype of ACLF (OR=2.491, 95%CI: 1.489-4.168, P=0.001), ACLF stage (OR=2.403, 95%CI: 1.687-3.421, P < 0.001), and urea(OR=2.567, 95%CI: 1.570-4.196, P < 0.001)were independently associated with AVB in ACLF patients. Conclusion AVB is an important influencing factor for the short-term survival of ACLF patients, and pleural effusion, AKI, BC subtype of ACLF, advanced ACLF, and urea are independent risk factors for the onset of AVB.
- Acute-On-Chronic Liver Failure /
- Varicose Veins /
- Risk Factors /
- Prognosis

HTML全文

图 1 AVB和预后的关系

注：a，30 d累积生存率生存曲线；b，180 d累积生存率生存曲线。

Figure 1. AVB and prognosis of ACLF

下载: 全尺寸图片幻灯片

表 1 1409例ACLF基线特征

Table 1. Baseline and clinical characteristics of 1409 cases of ACLF

指标	AVB组(n=167)	非AVB组(n=1242)	统计值	P值
年龄(岁)	46.48±9.37	46.70±9.97	t=0.079	0.778
性别[例(%)]			χ²=0.721	0.396
男	145(12.16)	1047(87.84)
女	22(10.14)	195(89.86)
ACLF分型[例(%)]			χ²=47.069	＜0.001
A型	20(4.17)	460(95.83)
B型	115(14.71)	667(85.29)
C型	32(21.77)	115(78.23)
ACLF分期[例(%)]			χ²=47.902	＜0.001
早期	3(8.82)	31(91.18)
中期	69(7.61)	838(92.39)
晚期	95(20.30)	373(79.70)
并发症[例(%)]
腹水	157(94.01)	1103(88.81)	χ²=3.683	0.055
胸腔积液	77(46.11)	373(30.03)	χ²=16.769	＜0.001
肺部感染	70(41.92)	196(15.78)	χ²=63.960	＜0.001
SBP	80(47.90)	373(30.03)	χ²=20.743	＜0.001
菌血症	24(14.37)	123(9.90)	χ²=3.145	0.076
肝性脑病	124(74.25)	446(35.91)	χ²=88.252	＜0.001
AKI	126(75.45)	497(40.02)	χ²=73.500	＜0.001
白蛋白(g/L)	28.89±5.73	31.20±4.26	t=6.134	0.013
TBil(μmol/L)	280.55(172.50~421.78)	284.25(194.93~388.43)	Z=0.260	0.795
PTA(%)	19.01±10.93	25.72±9.77	t=67.070	＜0.001
INR	2.07±0.54	2.07±0.61	t=0.011	0.917
血清钠(mmol/L)	132.47±5.87	133.29±5.89	t=2.861	0.091
胆碱酯酶(U/L)	2 583.30±1 420.97	2 770.91±1 404.29	t=2.056	0.040
纤维蛋白原(g/L)	1.68±0.90	1.74±0.96	t=0.568	0.451
血肌酐(μmol/L)	95.00(78.75~120.25)	89.00(78.00~105.00)	Z=2.740	0.006
血尿素(mmol/L)	12.65(7.98~21.04)	6.70(4.60~11.30)	Z=10.085	＜0.001
血清铁(μmol/L)	22.16±8.63	24.61±7.79	t=13.826	＜0.001
血红蛋白(g/L)	112.20(85.75~137.25)	121.70(104.00~139.00)	Z=3.512	＜0.001
血小板计数(×10⁹/L)	80.32±61.09	94.01±55.35	t=8.741	0.003
MELD评分	25.82±6.69	25.40±5.36	t=0.830	0.363
MELD-Na评分	31.93±11.21	29.93±9.82	t=5.875	0.015
30 d存活率(%)	43.42(66/152)	67.79(722/1065)	χ²=33.558	＜0.001
180 d存活率(%)	18.91(21/111)	53.97(421/780)	χ²=76.881	＜0.001

下载: 导出CSV

表 2 Logistic回归方程中的变量

Table 2. Variables in the equation for the multilevel Logistic regression

变量	回归系数	标准误	Wald值	自由度	P值	OR	95%CI
胸腔积液	0.420	0.179	5.491	1	0.019	1.522	1.071~2.162
ACLF分型B、C型	0.913	0.263	12.089	1	0.001	2.491	1.489~4.168
ACLF分期晚期	0.877	0.180	23.644	1	＜0.001	2.403	1.687~3.421
AKI	0.789	0.226	12.235	1	＜0.001	2.201	1.415~3.426
尿素	0.943	0.251	14.122	1	＜0.001	2.567	1.570~4.196
血小板计数	0.370	0.199	3.447	1	0.063	1.448	0.980~2.141
MELD-Na评分	-0.311	0.184	2.853	1	0.091	0.733	0.511~1.051

下载: 导出CSV

参考文献(20)

[1]	SARIN SK, CHOUDHURY A, SHARMA MK, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update[J]. Hepatol Int, 2019, 13(4): 353-390. DOI: 10.1007/s12072-019-09946-3.
[2]	JOSHI D, O'GRADY J, PATEL A, et al. Cerebral oedema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy[J]. Liver Int, 2014, 34(3): 362-366. DOI: 10.1111/liv.12257.
[3]	SHIN J, YU JH, JIN YJ, et al. Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding[J]. Clin Mol Hepatol, 2020, 26(4): 540-553. DOI: 10.3350/cmh.2020.0034.
[4]	TREBICKA J, GU W, IBÁÑEZ-SAMANIEGO L, et al. Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS[J]. J Hepatol, 2020, 73(5): 1082-1091. DOI: 10.1016/j.jhep.2020.04.024.
[5]	AL-MAHTAB M, AKBAR SM, GARG H. Influence of variceal bleeding on natural history of ACLF and management options[J]. Hepatol Int, 2016, 10(3): 436-439. DOI: 10.1007/s12072-015-9677-2.
[6]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Diagnostic and treatment guidelines for liver failure (2018 version)[J]. J Chin 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.
[7]	MOREAU R, JALAN R, GINES P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis[J]. Gastroenterology, 2013, 144(7): 1426-1437. e1-9. DOI: 10.1053/j.gastro.2013.02.042.
[8]	GARCIA-TSAO G, ABRALDES JG, BERZIGOTTI A, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases[J]. Hepatology, 2017, 65(1): 310-335. DOI: 10.1002/hep.28906.
[9]	HUANG Y, ZHANG W, XIANG H, et al. Treatment strategies in emergency endoscopy for acute esophageal variceal bleeding (CHESS1905): A Nationwide Cohort Study[J]. Front Med (Lausanne), 2022, 9: 872881. DOI: 10.3389/fmed.2022.872881.
[10]	KAMATH PS, KIM WR, Advanced Liver Disease Study Group. The model for end-stage liver disease (MELD)[J]. Hepatology, 2007, 45(3): 797-805. DOI: 10.1002/hep.21563.
[11]	KIM WR, BIGGINS SW, KREMERS WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list[J]. N Engl J Med, 2008, 359(10): 1018-1026. DOI: 10.1056/NEJMoa0801209.
[12]	GARG H, KUMAR A, GARG V, et al. Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure[J]. J Gastroenterol Hepatol, 2013, 28(8): 1361-1367. DOI: 10.1111/jgh.12191.
[13]	KAR R, KAR SS, SARIN SK. Hepatic coagulopathy-intricacies and challenges; a cross-sectional descriptive study of 110 patients from a superspecialty institute in North India with review of literature[J]. Blood Coagul Fibrinolysis, 2013, 24(2): 175-180. DOI: 10.1097/MBC.0b013e32835b2483.
[14]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis[J]. J Hepatol, 2018, 69(2): 406-460. DOI: 10.1016/j.jhep.2018.03.024.
[15]	AMITRANO L, GUARDASCIONE MA, MARTINO R, et al. Hypoxic hepatitis occurring in cirrhosis after variceal bleeding: still a lethal disease[J]. J Clin Gastroenterol, 2012, 46(7): 608-612. DOI: 10.1097/MCG.0b013e318254e9d4.
[16]	KUMAR A, DAS K, SHARMA P, et al. Hemodynamic studies in acute-on-chronic liver failure[J]. Dig Dis Sci, 2009, 54(4): 869-878. DOI: 10.1007/s10620-008-0421-9.
[17]	MEHTA G, MOOKERJEE RP, SHARMA V, et al. Systemic inflammation is associated with increased intrahepatic resistance and mortality in alcohol-related acute-on-chronic liver failure[J]. Liver Int, 2015, 35(3): 724-734. DOI: 10.1111/liv.12559.
[18]	TREBICKA J, GU W, IBÁÑEZ-SAMANIEGO L, et al. Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS[J]. J Hepatol, 2020, 73(5): 1082-1091. DOI: 10.1016/j.jhep.2020.04.024.
[19]	HEO NY. Acute-on-chronic liver failure: A predictor of poor prognosis in patients with variceal bleeding or a risk factor for variceal bleeding?[J]. Clin Mol Hepatol, 2020, 26(4): 487-488. DOI: 10.3350/cmh.2020.0209.
[20]	KUMAR R, KERBERT A, SHEIKH MF, et al. Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding[J]. J Hepatol, 2021, 74(1): 66-79. DOI: 10.1016/j.jhep.2020.06.010.