急性失代偿肝硬化患者全身炎症反应的研究进展

全卉; 江宇泳; 侯艺鑫; 姜婷婷; 王融冰

doi:10.3969/j.issn.1001-5256.2023.01.032

急性失代偿肝硬化患者全身炎症反应的研究进展

DOI: 10.3969/j.issn.1001-5256.2023.01.032

全卉^{1, 2},
江宇泳^1, , ,,
侯艺鑫¹,
姜婷婷¹,
王融冰¹

1.
首都医科大学附属北京地坛医院中西医结合中心，北京 100011
2.
北京中医药大学研究生院，北京 100011

基金项目:

首都卫生发展科研专项 (2020-2-2172);

北京中医药科技发展资金 (JJ2018-44);

王融冰全国名老中医工作室 (201612)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：全卉负责查找文献，撰写论文；侯艺鑫、姜婷婷负责查找文献，资料分析；江宇泳负责拟定写作思路，指导撰写文章并最后定稿；王融冰负责论文指导。

详细信息

通信作者:
江宇泳，jyuy11@126.com (ORCID: 0000-0002-6082-1180)

计量
- 文章访问数: 1759
- HTML全文浏览量: 1192
- PDF下载量: 75
- 被引次数: 0
出版历程
- 收稿日期: 2022-05-04
- 录用日期: 2022-06-10
- 出版日期: 2023-01-20

Research advances in systemic inflammatory response of acute decompensated cirrhosis patients

1.
Department of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100011, China
2.
Graduate School of Beijing University of Chinese Medicine, Beijing 100011, China

Research funding:

Capital Health Research and Development of Special (2020-2-2172);

Beijing TCM Science and Technology Development Fund (JJ2018-44);

Wang Rongbing Prestigious Traditional Chinese Medicine Physician Studio (201612)

More Information

Corresponding author: JIANG Yuyong, jyuy11@126.com (ORCID: 0000-0002-6082-1180)

摘要

摘要: 急性失代偿肝硬化是终末期肝病的一个阶段，该阶段患者经常出现失代偿并发症，病情进展较快。全身炎症反应以细菌感染局部组织后引起炎性因子过度分泌并迅速弥漫至全身，从而影响机体的生理活动、造成器官损伤或障碍为特征，是一种较严重的炎性状态。本综述从全身炎症的产生、影响全身炎症严重程度的因素、全身炎症在急性失代偿肝硬化的不同疾病阶段的表现，以及其在并发症中的作用进行了阐述，以期对全身炎症有更深入的了解，并能够将其应用于新的治疗和药物研发灵感中。
- 肝硬化 /
- 终末期肝病 /
- 细菌感染
Abstract: Acute decompensated cirrhosis is a stage of end-stage liver disease during which patients often experience decompensated complications and rapid progression. Systemic inflammatory response is characterized by excessive secretion of inflammatory factors caused by bacterial infection of local tissue and rapid spread to the whole body, thereby affecting the physiological activities of the body and causing organ damage or disorder, and it is a relatively serious inflammatory state. This article elaborates on the occurrence of systemic inflammation, the factors affecting the severity of systemic inflammation, the manifestation of systemic inflammation in different stages of decompensated cirrhosis, and the role of systemic inflammation in complications, in order to gain a deeper understanding of systemic inflammation and apply it in the research and development of new therapies and drugs.
- Liver Cirrhosis /
- End Stage Liver Disease /
- Bacterial Infections

HTML全文

参考文献(41)

[1]	MARTIN-MATEOS R, ALVAREZ-MON M, ALBILLOS A. Dysfunctional immune response in acute-on-chronic liver failure: It takes two to tango[J]. Front Immunol, 2019, 10: 973. DOI: 10.3389/fimmu.2019.00973.
[2]	GUSTOT T, STADLBAUER V, LALEMAN W, et al. Transition to decompensation and acute-on-chronic liver failure: Role of predisposing factors and precipitating events[J]. J Hepatol, 2021, 75(Suppl 1): S36-S48. DOI: 10.1016/j.jhep.2020.12.005.
[3]	ALBILLOS A, LARIO M, ÁLVAREZ-MON M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance[J]. J Hepatol, 2014, 61(6): 1385-1396. DOI: 10.1016/j.jhep.2014.08.010.
[4]	ARROYO V, ANGELI P, MOREAU R, et al. The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis[J]. J Hepatol, 2021, 74(3): 670-685. DOI: 10.1016/j.jhep.2020.11.048.
[5]	TREBICKA J, FERNANDEZ J, PAPP M, et al. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis[J]. J Hepatol, 2021, 74(5): 1097-1108. DOI: 10.1016/j.jhep.2020.11.019.
[6]	XU XY, DING HG, LI WG, et al. 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. 徐小元, 丁惠国, 李文刚, 等. 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.
[7]	XU X, TAN J, WANG H, et al. Risk stratification score to predict readmission of patients with acute decompensated cirrhosis within 90 days[J]. Front Med (Lausanne), 2021, 8: 646875. DOI: 10.3389/fmed.2021.646875.
[8]	D'AMICO G, PASTA L, MORABITO A, et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients[J]. Aliment Pharmacol Ther, 2014, 39(10): 1180-1193. DOI: 10.1111/apt.12721.
[9]	ZHANG DQ, ZHENG RD, LIN MH, et al. Influencing factors for the 90-day prognosis of patients with HBV-related acute-on-chronic liver failure[J]. J Clin Hepatol, 2021, 37(10): 2316-2319. DOI: 10.3969/j.issn.1001-5256.2021.10.011. 张冬青, 郑瑞丹, 林明华, 等. HBV相关慢加急性肝衰竭患者90天预后影响因素分析[J]. 临床肝胆病杂志, 2021, 37(10): 2316-2319. DOI: 10.3969/j.issn.1001-5256.2021.10.011.
[10]	IRVINE K, RATNASEKERA I, POWELL E, et al. Causes and consequences of innate immune dysfunction in cirrhosis[J]. Frontiers in immunology, 2019, 10: 293. DOI: 10.1371/ journal. pone. 0157371.
[11]	BERNARDI M, MOREAU R, ANGELI P, et al. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis[J]. J Hepatol, 2015, 63(5): 1272-1284. DOI: 10.1016/j.jhep.2015.07.004.
[12]	ALBILLOS A, MARTIN-MATEOS R, van der MERWE S, et al. Cirrhosis-associated immune dysfunction[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(2): 112-134. DOI: 10.1038/s41575-021-00520-7.
[13]	WIEST R, LAWSON M, GEUKING M. Pathological bacterial translocation in liver cirrhosis[J]. J Hepatol, 2014, 60(1): 197-209. DOI: 10.1016/j.jhep.2013.07.044.
[14]	TREBICKA J, MACNAUGHTAN J, SCHNABL B, et al. The microbiota in cirrhosis and its role in hepatic decompensation[J]. J Hepatol, 2021, 75(Suppl 1): S67-S81. DOI: 10.1016/j.jhep.2020.11.013.
[15]	ALBILLOS A, de LA HERA A, GONZÁLEZ M, et al. Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement[J]. Hepatology, 2003, 37(1): 208-217. DOI: 10.1053/jhep.2003.50038.
[16]	BAJAJ JS, THACKER LR, FAGAN A, et al. Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis[J]. JCI Insight, 2018, 3(5): e98019. DOI: 10.1172/jci.insight.98019.
[17]	MASLENNIKOV R, PAVLOV C, IVASHKIN V. Small intestinal bacterial overgrowth in cirrhosis: systematic review and meta-analysis[J]. Hepatol Int, 2018, 12(6): 567-576. DOI: 10.1007/s12072-018-9898-2.
[18]	SHAH A, SHANAHAN E, MACDONALD GA, et al. Systematic Review and Meta-Analysis: Prevalence of small intestinal bacterial overgrowth in chronic liver disease[J]. Semin Liver Dis, 2017, 37(4): 388-400. DOI: 10.1055/s-0037-1608832.
[19]	MUÑOZ L, ALBILLOS A, NIETO M, et al. Mesenteric Th1 polarization and monocyte TNF-alpha production: first steps to systemic inflammation in rats with cirrhosis[J]. Hepatology, 2005, 42(2): 411-419. DOI: 10.1002/hep.20799.
[20]	LI X, HE C, LI N, et al. The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice[J]. Gut Microbes, 2020, 11(6): 1774-1789. DOI: 10.1080/19490976.2020.1770042.
[21]	RAINER F, HORVATH A, SANDAHL TD, et al. Soluble CD163 and soluble mannose receptor predict survival and decompensation in patients with liver cirrhosis, and correlate with gut permeability and bacterial translocation[J]. Aliment Pharmacol Ther, 2018, 47(5): 657-664. DOI: 10.1111/apt.14474.
[22]	LECLERCQ S, CANI PD, NEYRINCK AM, et al. Role of intestinal permeability and inflammation in the biological and behavioral control of alcohol-dependent subjects[J]. Brain Behav Immun, 2012, 26(6): 911-918. DOI: 10.1016/j.bbi.2012.04.001.
[23]	LECLERCQ S, de SAEGER C, DELZENNE N, et al. Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence[J]. Biol Psychiatry, 2014, 76(9): 725-733. DOI: 10.1016/j.biopsych.2014.02.003.
[24]	MOOKERJEE RP, STADLBAUER V, LIDDER S, et al. Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome[J]. Hepatology, 2007, 46(3): 831-840. DOI: 10.1002/hep.21737.
[25]	KORF H, DU PLESSIS J, van PELT J, et al. Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity[J]. Gut, 2019, 68(10): 1872-1883. DOI: 10.1136/gutjnl-2018-316888
[26]	PIANO S, MORANDO F, CARRETTA G, et al. Predictors of early readmission in patients with cirrhosis after the resolution of bacterial infections[J]. Am J Gastroenterol, 2017, 112(10): 1575-1583. DOI: 10.1038/ajg.2017.253.
[27]	GRAUPERA I, SOLÀ E, FABRELLAS N, et al. Urine monocyte chemoattractant protein-1 is an independent predictive factor of hospital readmission and survival in cirrhosis[J]. PLoS One, 2016, 11(6): e0157371. DOI: 10.1371/journal.pone.0157371.
[28]	TREBICKA J, AMOROS A, PITARCH C, et al. Addressing profiles of systemic inflammation across the different clinical phenotypes of acutely decompensated cirrhosis[J]. Front Immunol, 2019, 10: 476. DOI: 10.3389/fimmu.2019.00476.
[29]	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.
[30]	CLÀRIA J, STAUBER RE, COENRAAD MJ, et al. Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure[J]. Hepatology, 2016, 64(4): 1249-1264. DOI: 10.1002/hep.28740.
[31]	van WYNGENE L, VANDEWALLE J, LIBERT C. Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?[J]. EMBO Mol Med, 2018, 10(8): e8712. DOI: 10.15252/emmm.201708712.
[32]	MOREAU R, CLÀRIA J, AGUILAR F, et al. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF[J]. J Hepatol, 2020, 72(4): 688-701. DOI: 10.1016/j.jhep.2019.11.009.
[33]	ZHANG IW, CURTO A, LÓPEZ-VICARIO C, et al. Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure[J]. J Hepatol, 2022, 76(1): 93-106. DOI: 10.1016/j.jhep.2021.08.009.
[34]	ENGELMANN C, CLÀRIA J, SZABO G, et al. Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction[J]. J Hepatol, 2021, 75(Suppl 1): S49-S66. DOI: 10.1016/j.jhep.2021.01.002.
[35]	BELLOT P, GARCÍA-PAGÁN JC, FRANCÉS R, et al. Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis[J]. Hepatology, 2010, 52(6): 2044-2052. DOI: 10.1002/hep.23918.
[36]	GINÈS P, KRAG A, ABRALDES JG, et al. Liver cirrhosis[J]. The Lancet, 2021, 398(10308): 1359-1376. DOI: 10.1016/S0140-6736(21)01374-X
[37]	YOTTI R, RIPOLL C, BENITO Y, et al. Left ventricular systolic function is associated with sympathetic nervous activity and markers of inflammation in cirrhosis[J]. Hepatology, 2017, 65(6): 2019-2030. DOI: 10.1002/hep.29104.
[38]	COSTA D, SIMBRUNNER B, JACHS M, et al. Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality[J]. J Hepatol, 2021, 74(4): 819-828. DOI: 10.1016/j.jhep.2020.10.004.
[39]	MENESES G, CÁRDENAS G, ESPINOSA A, et al. Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury[J]. Ann N Y Acad Sci, 2019, 1437(1): 43-56. DOI: 10.1111/nyas.13985.
[40]	REN C, YAO RQ, ZHANG H, et al. Sepsis-associated encephalopathy: a vicious cycle of immunosuppression[J]. J Neuroinflammation, 2020, 17(1): 14. DOI: 10.1186/s12974-020-1701-3.
[41]	IBIDAPO-OBE O, STENGEL S, KÖSE-VOGEL N, et al. Mucosal-associated invariant T cells redistribute to the peritoneal cavity during spontaneous bacterial peritonitis and contribute to peritoneal inflammation[J]. Cell Mol Gastroenterol Hepatol, 2020, 9(4): 661-677. DOI: 10.1016/j.jcmgh.2020.01.003.