肝硬化患者发生隐匿性肝性脑病的危险因素及预后分析

刘思琴; 王小梅; 李霞; 梁露文; 王可; 王瑞

doi:10.3969/j.issn.1001-5256.2022.02.020

肝硬化患者发生隐匿性肝性脑病的危险因素及预后分析

DOI: 10.3969/j.issn.1001-5256.2022.02.020

刘思琴^a,
王小梅^a, ,,
李霞^b,
梁露文^c,
王可^a,
王瑞^a

a.
重庆医科大学附属第二医院肝胆外科，重庆 400010
b.
重庆医科大学附属第二医院消化内科，重庆 400010
c.
重庆医科大学附属第二医院感染病科，重庆 400010

基金项目:

2019年重庆市科委技术创新与应用发展项目 (cstc2019jscx-msxmX0117)

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：刘思琴负责课题设计，资料分析，撰写论文；李霞、梁露文、王可、王瑞参与了项目实施和收集数据，修改论文以及进行统计复核；王小梅负责拟定写作思路，指导撰写文章并最后定稿。所有作者均参与了稿件的讨论、解释、修订和最终批准。

详细信息

通信作者:
王小梅，300394@hospital.cqmu.edu.cn

计量
- 文章访问数: 432
- HTML全文浏览量: 136
- PDF下载量: 55
- 被引次数: 0
出版历程
- 收稿日期: 2021-06-22
- 录用日期: 2021-08-12
- 出版日期: 2022-02-20

Covert hepatic encephalopathy in liver cirrhosis: Risk factors and prognosis

a.
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
b.
Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
c.
Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China

Research funding:

2019 Chongqing Technology Innovation and Application Development Project (cstc2019jscx-msxmX0117)

More Information

Corresponding author: WANG Xiaomei, 300394@hospital.cqmu.edu.cn

摘要

摘要: 目的探讨肝硬化患者发生隐匿性肝性脑病(CHE)的危险因素，并分析其对预后的影响。方法选择2019年9月—2020年6月重庆市某三甲医院的416例肝硬化患者为研究对象，根据是否发生CHE分为CHE组(n=212)和非CHE组(n=204)，收集临床资料和实验室检查结果，并实施6个月随访。正态分布的计量资料两组间比较采用t检验，不服从正态分布的计量资料两组间比较采用Mann-Whitney U检验；计数资料两组间比较采用χ²检验、连续校正χ²检验或Mann-Whitney U检验。经单因素和多因素logistic回归分析发生CHE的危险因素。结果 CHE的发生率为51%，单因素分析发现年龄、病程、HE病史、感染、腹水、电解质紊乱、肝肾综合征、Child-Pugh肝功能分级、凝血酶原时间、总胆红素、肌酐、血小板、凝血酶原活动度、白蛋白、MELD评分等是CHE的影响因素(P值均＜0.05)；多因素分析表明HE病史(OR=10.848，95%CI：4.971~23.674)、经颈静脉肝内门体分流术(TIPS)(OR=4.334，95%CI：1.203~15.621)、Child-Pugh肝功能分级(OR=4.968, 95%CI：1.299~18.992)、MELD评分(OR=1.253，95%CI：1.161~1.352)是CHE的独立预测因子(P值均＜0.05)；CHE组患者的中短期再入院、HE和死亡发生率均高于非CHE组(P值均＜0.05)。结论 CHE发生率较高，且影响患者预后，既往HE病史、TIPS术后、Child-Pugh分级C级和MELD评分较高的患者应警惕CHE的发生，早发现、早筛查、早干预，以最大限度改善肝硬化患者预后。
- 肝性脑病 /
- 肝硬化 /
- 危险因素 /
- 预后
Abstract: Objective To investigate the risk factors for covert hepatic encephalopathy (CHE) in patients with liver cirrhosis and their influence on prognosis. Methods A total of 416 patients with liver cirrhosis who were hospitalized in a grade A tertiary hospital in Chongqing from September 2019 to June 2020 were enrolled in the study, and according to the presence or absence of CHE, they were divided into CHE group with 212 patients and non-CHE group with 204 patients. Clinical data and laboratory examination results were collected, and follow-up was performed for 6 months. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test, the continuous correction chi-square test, and the Mann-Whitney U test were used for comparison of categorical data between groups. Univariate and multivariate logistic regression analyses were used to analyze the risk factors for CHE. Results The incidence rate of CHE was 51%. The univariate analysis showed that age, course of disease, the medical history of hepatic encephalopathy (HE), infection, ascites, electrolyte disturbance, hepatorenal syndrome, Child-Pugh class, prothrombin time, total bilirubin, creatinine, platelet, prothrombin activity, albumin, and Model for End-stage Liver Disease (MELD) score were the influencing factors for CHE (all P < 0.05). The multivariate logistic regression analysis showed that the medical history of HE (OR=10.848, 95% CI: 4.971-23.674, P < 0.05), transjugular intrahepatic portosystemic shunt (TIPS) (OR=4.334, 95%CI: 1.203-15.621, P < 0.05), Child-Pugh class (OR=4.968, 95%CI: 1.299-18.992, P < 0.05), and MELD score (OR=1.253, 95%CI: 1.161-1.352, P < 0.05) were independent predictive factors for CHE (P < 0.05). The follow-up study showed that CHE had an effect on the short-or medium-term readmission, HE, and death of patients (all P < 0.05). Conclusion CHE has a relatively high incidence rate and greatly affects the prognosis of patients with liver cirrhosis. The development of CHE should be taken seriously in patients with a past history of HE, a history of TIPS, Child-Pugh class C liver function, and a high MELD score, and identification, screening, and intervention should be performed as early as possible to improve the prognosis of patients with liver cirrhosis.
- Hepatic Encephalopathy /
- Liver Cirrhosis /
- Risk Factors /
- Prognosis

HTML全文

表 1 肝硬化患者发生CHE的单因素分析

变量	CHE组(n=212)	非CHE组(n=204)	统计值	P值
年龄(岁)	56(49~66)	51(46~57)	Z=-5.274	＜0.001
性别(例)			χ²=2.018	0.155
男	147	128
女	65	76
BMI(kg/m²)	23.17(20.96~25.25)	22.78(20.79~24.76)	Z=-9.410	0.347
HE病史(例)			χ²=63.391	＜0.001
有	78	10
无	134	194
病程(例)			χ²=4.488	0.034
代偿期	4	12
失代偿期	208	192
TIPS术后(例)			χ²=9.757	0.002
是	19	4
否	193	200
人工肝(例)			χ²=2.158¹⁾	0.142
有	4	0
无	208	204
肝肾综合征(例)			χ²=8.192	0.004
是	11	1
否	201	203
合并感染(例)			χ²=18.791	＜0.001
有	101	55
无	111	149
低钠血症(例)			χ²=6.989	0.008
是	14	3
否	198	201
低钾血症(例)			χ²=1.741	0.187
有	53	40
无	159	164
病因(例)			χ²=9.495	0.053
病毒性	158	152
胆汁性	11	12
酒精性	36	21
免疫性	7	19
腹水(例)			χ²=21.903	＜0.001
无	96	134
小	69	47
中	17	14
大	30	9
肝功能分级(例)			χ²=56.950	＜0.001
A级	86	150
B级	88	51
C级	38	3
凝血酶原时间(s)	16.90(15.03~18.90)	15.60(14.40~17.16)	Z=-4.953	＜0.001
球蛋白(g/L)	29.20(25.03~35.25)	30.60(25.53~35.95)	Z=-0.939	0.348
总胆红素(g/L)	40.75(31.76~53.38)	29.00(24.23~37.40)	Z=-7.625	＜0.001
白蛋白(g/L)	32.75(27.75~37.20)	35.20(30.25~39.49)	Z=-3.570	＜0.001
肌酐(μmol/L)	72.80(64.08~86.98)	64.80(57.73~73.48)	Z=-5.380	＜0.001
血小板(×10⁹/L)	60.00(44.00~100.00)	73.50(46.00~125.00)	Z=-2.317	0.020
血糖(mmol/L)	5.64(4.87~7.02)	5.47(4.72~6.29)	Z=-2.060	0.039
ALT(U/L)	25.00(17.25~41.00)	28.00(18.00~47.00)	Z=-1.568	0.117
AST(U/L)	38.00(27.25~59.00)	35.50(26.00~57.75)	Z=-0.702	0.483
凝血酶原活动度(%)	64.50(52.25~79.00)	73.00(63.00~86.00)	Z=-4.586	＜0.001
血细胞计数(×10⁹/L)	3.99(2.96~5.76)	3.92(2.94~5.53)	Z=-0.204	0.839
MELD评分	10.83(7.82~14.67)	7.33(5.48~9.36)	Z=-8.249	＜0.001
国际标准化比值	1.42(1.24~1.61)	1.27(1.17~1.42)	Z=-5.053	＜0.001
注：1)连续校正χ²检验。

下载: 导出CSV

表 2 肝硬化患者CHE危险因素的logistic回归分析

变量	回归系数	SE	Wald	P值	OR	95%CI
HE病史(0=无；1=有)	2.384	0.398	35.845	＜0.001	10.848	4.971~23.674
TIPS术(0=无；1=有)	1.467	0.654	5.026	0.025	4.334	1.203~15.621
肝功能分级(1=A级；2=B级；3=C级)			7.130	0.028
B级	0.463	0.271	2.908	0.088	1.589	0.933~2.705
C级	1.603	0.684	5.488	0.019	4.968	1.299~18.992
年龄	0.047	0.012	15.029	＜0.001	1.048	1.024~1.074
MELD评分	0.225	0.039	33.878	＜0.001	1.253	1.161~1.352
常数	-5.312	0.783	46.072	＜0.001	0.005

下载: 导出CSV

表 3 CHE对患者预后情况比较

组别	例数	再入院	HE	死亡
CHE组[例(%)]	193	138(71.5)	45(23.3)	12(6.2)
非CHE组[例(%)]	162	30(18.5)	3(1.9)	2(1.2)
χ²值		99.184	34.702	5.773
P值		＜0.001	＜0.001	0.016

下载: 导出CSV

表 4 不同组别CHE患者的预后分析

变量	HE组(n=48)	非HE组(n=145)	统计值	P值
肝功能分级[例(%)]			Z=7.949	0.019
A级	6(12.5)	63(43.4)
B级	19(39.6)	62(42.8)
C级	23(47.9)	20(13.8)
HE病史[例(%)]			χ²=12.941	＜0.001
是	30(62.5)	48(33.1)
否	18(37.5)	97(66.9)
TIPS[例(%)]			χ²=0.099¹⁾	0.753
是	5(10.4)	11(7.6)
否	43(89.6)	134(92.4)
MELD评分	13.76±6.38	10.39±4.26	t=-4.164	＜0.001
注：1)连续校正χ²检验。

下载: 导出CSV

参考文献(26)

[1]	XU L, LI M, NAN SY. Study on illness uncertainty and influential factors of inpatients with cirrhosis and their family caregivers[J]. Chin J Nurs, 2020, 55(8): 1206-1211. DOI: 10.3761/j.issn.0254-1769.2020.08.018. 许丽, 李萌, 南士英. 肝硬化住院患者及家属疾病不确定感现状及影响因素的研究[J]. 中华护理杂志, 2020, 55(8): 1206-1211. DOI: 10.3761/j.issn.0254-1769.2020.08.018.
[2]	ELWIR S, RAHIMI RS. Hepatic encephalopathy: An update on the pathophysiology and therapeutic options[J]. J Clin Transl Hepatol, 2017, 5(2): 142-151. DOI: 10.14218/JCTH.2016.00069.
[3]	HU XP, GAO J. International normalized ratio and model for end-stage liver disease score for predicting short-term prognosis of cirrhotic patients with hepatic encephalopathy[J]. J Third Milit Med Univ, 2019, 41(14): 1374-1380. DOI: 10.16016/j.1000-5404.201901232. 胡小鹏, 高建. 国际标准化比值和终末期肝病模型评分对并发肝性脑病的肝硬化患者短期预后的预测价值[J]. 第三军医大学学报, 2019, 41(14): 1374-1380. DOI: 10.16016/j.1000-5404.201901232.
[4]	VILSTRUP H, AMODIO P, BAJAJ J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European[J]. Hepatology, 2014, 60(2): 715-735. DOI: 10.1002/hep.27210.
[5]	AGRAWAL S, UMAPATHY S, DHIMAN RK. Minimal hepatic encephalopathy impairs quality of life[J]. J Clin Exp Hepatol, 2015, 5(Suppl 1): S42-S48. DOI: 10.1016/j.jceh.2014.11.006.
[6]	LIAO W, TANG Y, WANG CY, et al. Sleep and cognition and risk factors in patients with hepatitis B cirrhosis complicated with occult hepatic encephalopathy[J]. Clin J Med Offic, 2020, 48(4): 420-421. DOI: 10.16680/j.1671-3826.2020.04.21. 廖威, 唐艳, 王春燕, 等. 乙肝肝硬化合并隐匿性肝性脑病患者睡眠和认知情况及危险因素研究[J]. 临床军医杂志, 2020, 48(4): 420-421. DOI: 10.16680/j.1671-3826.2020.04.21.
[7]	STEPANOVA M, MISHRA A, VENKATESAN C, et al. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009[J]. Clin Gastroenterol Hepatol, 2012, 10(9): 1034-1041. e1. DOI: 10.1016/j.cgh.2012.05.016.
[8]	PÉREZ-MATOS MC, JIANG ZG, TAPPER EB. Factors that affect results of psychometric tests to identify patients with minimal hepatic encephalopathy[J]. Clin Gastroenterol Hepatol, 2018, 16(11): 1836-1838. DOI: 10.1016/j.cgh.2018.03.010.
[9]	STINTON LM, JAYAKUMAR S. Minimal hepatic encephalopathy[J]. Can J Gastroenterol, 2013, 27(10): 572-574. DOI: 10.1155/2013/547670.
[10]	NABI E, THACKER LR, WADE JB, et al. Diagnosis of covert hepatic encephalopathy without specialized tests[J]. Clin Gastroenterol Hepatol, 2014, 12(8): 1384-1389. e2. DOI: 10.1016/j.cgh.2013.12.020.
[11]	LABENZ C, BEUL L, TOENGES G, et al. Validation of the simplified Animal Naming Test as primary screening tool for the diagnosis of covert hepatic encephalopathy[J]. Eur J Intern Med, 2019, 60: 96-100. DOI: 10.1016/j.ejim.2018.08.008.
[12]	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.
[13]	Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the management of hepatic encephalopathy in cirrhosis[J]. J Clin Hepatol, 2018, 34(10): 2076-2089. DOI: 10.3969/j.issn.1001-5256.2018.10.007. 中华医学会肝病学分会. 肝硬化肝性脑病诊疗指南[J]. 临床肝胆病杂志, 2018, 34(10): 2076-2089. DOI: 10.3969/j.issn.1001-5256.2018.10.007.
[14]	LI SW, WANG K, YU YQ, et al. Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China[J]. World J Gastroenterol, 2013, 19(46): 8745-8751. DOI: 10.3748/wjg.v19.i46.8745.
[15]	ZENG X, LI XX, SHI PM, et al. Utility of the EncephalApp Stroop Test for covert hepatic encephalopathy screening in Chinese cirrhotic patients[J]. J Gastroenterol Hepatol, 2019, 34(10): 1843-1850. DOI: 10.1111/jgh.14656.
[16]	QIAN ZP, YANG Y. Study on the current situation and risk factors of minimal hepatic encephalopathy in patients with liver cirrhosis[J]. Chin J Nurs, 2020, 55(6): 872-876. DOI: 10.376l/-issn.0254-1769.2020.06.015. 钱珠萍, 杨艳. 肝硬化患者发生轻微型肝性脑病现状及影响因素研究[J]. 中华护理杂志, 2020, 55(6): 872-876. DOI: 10.376l/-issn.0254-1769.2020.06.015.
[17]	MINA A, MORAN S, ORTIZ-OLVERA N, et al. Prevalence of minimal hepatic encephalopathy and quality of life in patients with decompensated cirrhosis[J]. Hepatol Res, 2014, 44(10): E92-E99. DOI: 10.1111/hepr.12227.
[18]	AMPUERO J, MONTOLIÚ C, SIMÓN-TALERO M, et al. Minimal hepatic encephalopathy identifies patients at risk of faster cirrhosis progression[J]. J Gastroenterol Hepatol, 2018, 33(3): 718-725. DOI: 10.1111/jgh.13917.
[19]	PERAZZO JC, TALLIS S, DELFANTE A, et al. Hepatic encephalopathy: An approach to its multiple pathophysiological features[J]. World J Hepatol, 2012, 4(3): 50-65. DOI: 10.4254/wjh.v4.i3.50.
[20]	SAAB S. Evaluation of the impact of rehospitalization in the management of hepatic encephalopathy[J]. Int J Gen Med, 2015, 8: 165-173. DOI: 10.2147/IJGM.S81878.
[21]	WANG AJ, PENG AP, LI BM, et al. Natural history of covert hepatic encephalopathy: An observational study of 366 cirrhotic patients[J]. World J Gastroenterol, 2017, 23(34): 6321-6329. DOI: 10.3748/wjg.v23.i34.6321.
[22]	YOSHIMURA E, ICHIKAWA T, MIYAAKI H, et al. Screening for minimal hepatic encephalopathy in patients with cirrhosis by cirrhosis-related symptoms and a history of overt hepatic encephalopathy[J]. Biomed Rep, 2016, 5(2): 193-198. DOI: 10.3892/br.2016.702.
[23]	RIGGIO O, AMODIO P, FARCOMENI A, et al. A model for predicting development of overt hepatic encephalopathy in patients with cirrhosis[J]. Clin Gastroenterol Hepatol, 2015, 13(7): 1346-1352. DOI: 10.1016/j.cgh.2014.12.025.
[24]	LABENZ C, TOENGES G, HUBER Y, et al. Development and validation of a prognostic score to predict covert hepatic encephalopathy in patients with cirrhosis[J]. Am J Gastroenterol, 2019, 114(5): 764-770. DOI: 10.14309/ajg.0000000000000121.
[25]	TAPPER EB, PARIKH ND, SENGUPTA N, et al. A risk score to predict the development of hepatic encephalopathy in a population-based cohort of patients with cirrhosis[J]. Hepatology, 2018, 68(4): 1498-1507. DOI: 10.1002/hep.29628.
[26]	BALE A, PAI CG, SHETTY S, et al. Prevalence of and factors associated with minimal hepatic encephalopathy in patients with cirrhosis of liver[J]. J Clin Exp Hepatol, 2018, 8(2): 156-161. DOI: 10.1016/j.jceh.2017.06.005.