慢加急性肝衰竭合并细菌感染患者的临床特征及预后影响因素分析

刘晓燕; 胡瑾华; 李晨; 陈婧; 童晶晶; 关崇丹; 彭宇辉; 宁鹏; 严立龙; 苏海滨

doi:10.3969/j.issn.1001-5256.2021.09.028

慢加急性肝衰竭合并细菌感染患者的临床特征及预后影响因素分析

DOI: 10.3969/j.issn.1001-5256.2021.09.028

解放军总医院第五医学中心肝病学部，北京 100039

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：苏海滨、刘晓燕负责课题设计，资料分析，撰写论文；胡瑾华、李晨、童晶晶、关崇丹、彭宇辉、宁鹏、严立龙、陈婧参与收集和整理数据；苏海滨负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
苏海滨，sunhaibin302@163.com

中图分类号: R575.3
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出版历程
- 收稿日期: 2021-01-17
- 录用日期: 2021-02-03
- 出版日期: 2021-09-20

Clinical features of patients with acute-on-chronic liver failure and bacterial infection and influencing factors for prognosis

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

摘要

摘要: 目的研究慢加急性肝衰竭(ACLF)合并细菌感染患者的临床感染特点及90 d生存率的相关影响因素。方法选取2014年1月—2015年12月解放军总医院第五医学中心收治的ACLF患者，收集和分析患者的相关临床资料：感染时间及部位、微生物培养情况、生化及炎性指标、合并感染后28 d及90 d预后情况等。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。应用寿命表法绘制生存曲线。将单因素分析中对预后有影响的指标进一步行多因素logistic回归分析。结果共收治ACLF患者1074例，其中609例合并细菌感染，感染发生率为56.7%。有16例患者在90 d内行肝移植手术，其余593例均完成了相关数据统计。各部位感染占总感染人数比例分别为：腹腔70.15%、肺部41.15%、败血症11.97%、泌尿系统5.40%、胸腔4.89%，其他部位8.6%。64.76%的患者为单部位感染。微生物培养阳性率分别为：腹水22.70%、痰52.82%、尿40.63%、胸水35.71%。腹水中大肠埃希菌占首位(43.82%)；痰液中肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌分别占22.67%、24.00%、22.67%；血培养中大肠埃希菌和肺炎克雷伯菌分别占33.80%、29.58%，其次为葡萄球菌(15.49%)。ACLF合并细菌感染后90 d生存率为38.11%(226/593)，多因素logistic回归分析结果显示年龄(P=0.006)、肝性脑病分期(P＜0.001)、肝衰竭分期(P＜0.001)和急性肾损伤(P＜0.001)是影响ACLF合并细菌感染患者90 d生存的独立危险因素。结论 ACLF合并细菌感染发生率高，90 d生存率较低，出现急性肾损伤、Ⅲ期以上肝性脑病或肝衰竭晚期时提示预后差。
- 慢加急性肝功能衰竭 /
- 细菌感染 /
- 预后
Abstract: Objective To investigate the clinical features of infection in patients with acute-on-chronic liver failure (ACLF) and bacterial infection and the influencing factors for 90-day survival rate. Methods The patients with ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to December 2015 were enrolled, and related clinical data were collected and analyzed, including infection time and site, microbial culture, biochemical parameters and inflammatory markers, and 28- and 90-day prognosis after infection. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The life-table method was used to plot survival curves. The indices affecting prognosis in the univariate analysis were further included in the multivariate logistic regression analysis. Results A total of 1074 patients with ACLF were admitted, among whom 609 had bacterial infection, and the incidence rate of bacterial infection was 56.7%. Among these 609 patients, 16 underwent liver transplantation within 90 days and related data statistics were obtained for the remaining 593 patients. As for infection site, among the patients with infection, 70.15% had abdominal infection, 41.15% had pulmonary infection, 11.97% had sepsis, 5.40% had urinary system infection, 4.89% had thoracic infection, and 8.6% had infection at other sites. Among the patients with infection, 64.76% had infection at a single site. The positive rates of microbial culture of ascites, phlegm, urine, and pleural effusion were 22.70%, 52.82%, 40.63%, and 35.71%, respectively. Escherichia coli was the most common bacterium in ascites and accounted for 43.82%; Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii accounted for 22.67%, 24.00%, and 22.67%, respectively, in phlegm; Escherichia coli, Klebsiella pneumoniae, and Staphylococcaceae accounted for 33.80%, 29.58%, and 15.49%, respectively, in blood culture. The 90-day survival rate after infection was 38.11% (226/593) in the patients with ACLF, and the multivariate logistic regression analysis showed that age (P=0.006), stage of hepatic encephalopathy (HE) (P < 0.001), stage of liver failure (P < 0.001), and acute kidney injury (AKI) (P < 0.001) were independent risk factors for 90-day survival in patients with ACLF and infection. Conclusion There is a high incidence rate of infection in patients with ACLF. The 90-day survival rate is relatively low, and the presence of AKI, HE stage III or above, and advanced liver failure may indicate poor prognosis.
- Acute-On-Chronic Liver Failure /
- Bacterial Infections /
- Prognosis

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图 1 诊断ACLF合并细菌感染后生存曲线

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表 2 不同部位细菌培养阳性情况

细菌	腹腔感染(n=89)	肺炎(n=75)	败血症(n=71)	尿路感染(n=13)	胸腔感染(n=9)
革兰阴性菌[例(%)]
大肠埃希菌	39(43.82)	4(5.33)	24(33.80)	3(23.08)	2(22.22)
肺炎克雷伯菌	8(8.99)	17(22.67)	21(29.58)	0	4(44.44)
铜绿假单胞菌	0	18(24.00)	2(2.82)	0	0
鲍曼不动杆菌	4(4.49)	17(22.67)	3(4.23)	0	0
嗜麦芽寡养单胞菌	0	8(10.67)	3(4.23)	0	0
其他	6(6.74)	0	2(2.82)	2(15.38)	0
革兰阳性菌[例(%)]
链球菌	5(5.62)	4(5.33)	3(4.23)	0	1(11.11)
葡萄球菌	10(11.24)	7(9.33)	11(15.49)	2(15.38)	1(11.11)
肠球菌	12(13.48)	0	0	6(46.15)	2(22.22)
其他	5(5.62)	0	2(2.82)	0	0

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表 3 生存组和死亡组单因素分析结果

指标	存活组(n=226)	死亡组(n=367)	统计值	P值
男/女(例)	189/37	295/72	χ²=0.983	0.321
年龄(岁)	47.38±10.68	51.49±11.89	t=4.248	＜0.001
病因(HBV/酒精/自身免疫性/药物/其他，例)	159/45/10/1/11	229/76/19/13/30	χ²=18.732	0.002
肝硬化(有/无，例)	199/27	326/41	χ²=0.083	0.774
感染部位(单/多，例)	178/48	206/161	χ²=593.000	＜0.001
腹水(有/无，例)	223/3	362/5	χ²=0.001	0.970
肝性脑病(无、Ⅰ/Ⅱ期、Ⅲ/Ⅳ期，例)	167/48/11	138/97/132	χ²=29.907	＜0.001
肺部感染(有/无，例)	57/169	187/180	χ²=38.250	＜0.001
自发性腹膜炎(有/无，例)	169/57	247/120	χ²=3.730	0.050
上消化道出血(有/无，例)	15/211	68/299	χ²=16.430	＜0.001
败血症(有/无，例)	26/200	45/322	χ²=0.076	0.780
胸腔感染(有/无，例)	5/221	24/343	χ²=5.130	0.020
国际标准化比值	1.85±0.44	2.56±1.21	χ²=-8.460	＜0.001
总胆红素(μmol/L)	303.27±137.06	335.81±158.53	t=-2.597	0.010
血肌酐(μmol/L)	106.70±67.63	152.48±125.37	t=-6.165	＜0.001
白细胞(×10⁹/L)	7.00(4.75~9.68)	8.34(5.43~13.07)	Z=-3.883	＜0.001
中性粒细胞(×10⁹/L)	4.87(3.01~7.41)	6.18(3.78~10.48)	Z=-4.645	＜0.001
降钙素原(ng/ml)	0.70(0.39~1.45)	0.79(0.42~1.91)	Z=-1.955	0.050
C反应蛋白(g/L)	16.78(9.28~36.30)	17.60(9.64~36.11)	Z=-0.937	0.349
乳酸(mmol/L)	1.56(1.25~2.01)	1.69(1.28~2.73)	Z=-1.837	0.066
肝衰竭分期(早期/中期/晚期，例)	195/25/6	73/170/124	χ²=59.300	＜0.001
MELD评分	22.71±6.18	27.99±8.29	t=-7.971	＜0.001

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表 4 影响ACLF合并感染患者90 d生存的多因素logistic回归分析

指标	B值	SE	Wald	Exp(B)	95%CI	P值
年龄	-0.038	0.014	7.442	0.963	0.937~0.989	0.006
自发性腹膜炎	-0.214	0.440	0.236	0.807	0.341~1.913	0.627
肝性脑病分期			23.332			＜0.001
Ⅰ/Ⅱ期vs无	2.409	0.508	22.523	11.128	4.114~30.099	＜0.001
Ⅲ/Ⅳ期vs无	1.860	0.546	11.603	6.427	2.203~18.747	0.001
急性肾损伤	-1.288	0.315	16.744	0.276	0.149~0.511	＜0.001
白细胞	-0.014	0.024	0.366	0.986	0.941~1.032	0.545
总胆红素	-0.001	0.001	1.183	0.999	0.997~1.001	0.277
血肌酐	0.000	0.002	0.017	1.000	0.996~1.003	0.896
肝衰竭分期			19.104			＜0.001
中期vs早期	1.954	0.449	18.933	7.057	2.927~17.017	＜0.001
晚期vs早期	1.463	0.466	9.838	4.318	1.731~10.772	0.002
降钙素原	-0.101	0.063	2.633	0.903	0.799~1.021	0.105
常量	-1.153	1.023	1.270	0.316		0.260

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参考文献(14)

[1]	LIU XY, CHEN J, TONG JJ, et al. The causes of death and clinical characteristic of patients with HBV-ACLF[J]. Chin J Hepatol, 2015, 23(9): 704-706. DOI: 10.3760/cma.j.issn.1007-3418.2015.09.015. 刘晓燕, 陈婧, 童晶晶, 等. 393例乙型肝炎病毒相关慢加急性肝衰竭死亡患者死因及临床特征分析[J]. 中华肝脏病杂志, 2015, 23(9): 704-706. DOI: 10.3760/cma.j.issn.1007-3418.2015.09.015.
[2]	BAJAJ JS, O'LEARY JG, REDDY KR, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures[J]. Hepatology, 2014, 60(1): 250-256. DOI: 10.1002/hep.27077.
[3]	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. DOI: 10.1053/j.gastro.2013.02.042.
[4]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, CMA; Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, CMA. Guideline for diagnosis and treatment of liver failure (2012 version)[J]. Chin J Clin Infect Dis, 2012, 5(6): 321-327. DOI: 10.3760/cma.j.issn.1674-2397.2012.06.001. 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(2012年版)[J]. 中华临床感染病杂志, 2012, 5(6): 321-327. DOI: 10.3760/cma.j.issn.1674-2397.2012.06.001.
[5]	Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the management of ascites and complications in cirrhosis[J]. J Clin Hepatol, 2017, 33(10): 1847-1863. DOI: 10.3969/j.issn.1001-5256.2017.10.003. 中华医学会肝病学分会. 肝硬化腹水及相关并发症的诊疗指南[J]. 临床肝胆病杂志, 2017, 33(10): 1847-1863. DOI: 10.3969/j.issn.1001-5256.2017.10.003.
[6]	ANGELI P, GINÈS P, WONG F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: Revised consensus recommendations of the International Club of Ascites[J]. J Hepatol, 2015, 62(4): 968-974. DOI: 10.1016/j.jhep.2014.12.029.
[7]	Society of Infectious Diseases, Chinese Medical Association. Expert consensus on diagnosis and treatment of end-stage liver disease complicated with infections[J]. J Clin Hepatol, 2018, 34(9): 1862-1872. DOI: 10.3969/j.issn.1001-5256.2018.09.008. 中华医学会感染病学分会. 终末期肝病合并感染诊治专家共识[J]. 临床肝胆病杂志, 2018, 34(9): 1862-1872. DOI: 10.3969/j.issn.1001-5256.2018.09.008.
[8]	FERNÁNDEZ J, ACEVEDO J, WIEST R, et al. Bacterial and fungal infections in acute-on-chronic liver failure: Prevalence, characteristics and impact on prognosis[J]. Gut, 2018, 67(10): 1870-1880. DOI: 10.1136/gutjnl-2017-314240.
[9]	ARVANITI V, D'AMICO G, FEDE G, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis[J]. Gastroenterology, 2010, 139(4): 1246-1256. DOI: 10.1053/j.gastro.2010.06.019.
[10]	JALAN R, FERNANDEZ J, WIEST R, et al. Bacterial infections in cirrhosis: A position statement based on the EASL Special Conference 2013[J]. J Hepatol, 2014, 60(6): 1310-1324. DOI: 10.1016/j.jhep.2014.01.024.
[11]	BAJAJ JS, O'LEARY JG, TANDON P, et al. Hepatic encephalopathy is associated with mortality in patients with cirrhosis independent of other extrahepatic organ failures[J]. Clin Gastroenterol Hepatol, 2017, 15(4): 565-574. DOI: 10.1016/j.cgh.2016.09.157.
[12]	LIU XY, XIN SJ, CHEN J, et al. Significance of liver failure staging in predicting the prognosis of HBV-acute-on-chronic liver failure[J]. Acad J Chin PLA Med Sch, 2014, 35(6): 521-524, 544. DOI: 10.3969/j.issn.2095-5227.2014.06.001. 刘晓燕, 辛绍杰, 陈婧, 等. 肝衰竭分期对HBV感染慢加急性肝衰竭预后判断的意义[J]. 解放军医学院学报, 2014, 35(6): 521-524, 544. DOI: 10.3969/j.issn.2095-5227.2014.06.001.
[13]	GUPTA S, JASWANI P, SHARMA RK, et al. Procalcitonin as a diagnostic biomarker of sepsis: A tertiary care centre experience[J]. J Infect Public Health, 2019, 12(3): 323-329. DOI: 10.1016/j.jiph.2018.11.004.
[14]	CHOI JJ, MCCARTHY MW. Novel applications for serum procalcitonin testing in clinical practice[J]. Expert Rev Mol Diagn, 2018, 18(1): 27-34. DOI: 10.1080/14737159.2018.1407244.