炎症反应在慢加急性肝衰竭中的作用及治疗策略
DOI: 10.3969/j.issn.1001-5256.2022.08.041
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:徐华谦参与拟定写作思路,收集分析文献,论文撰写及修改;李雪参与指导撰写文章及论文修改;汤善宏负责拟定写作思路,指导撰写文章与最后定稿。
Research advances in the role of inflammatory response and related treatment strategies in acute-on-chronic liver failure
-
摘要: 慢加急性肝衰竭(ACLF)是在慢性肝病基础上,由一系列诱因导致肝功能迅速恶化的临床综合征,以多器官衰竭和短期高病死率为突出特征。系统性炎症的发生是ACLF疾病进展的重要影响因素之一,是机体对感染的自然防御,但当炎症介质过度释放打破原有的“促炎和抗炎”动态平衡,反而会加重肝损伤甚至发生失代偿。因此,炎症反应的强度与ACLF患者预后密切相关,但目前对于炎症反应对ACLF患者的影响以及如何应对炎症风暴的关注度还不够,故本文归纳了目前炎症反应对ACLF的影响及其治疗进展,为临床中ACLF的诊疗提供思路。Abstract: Acute-on-chronic liver failure (ACLF) is a clinical syndrome with rapid deterioration of liver function caused by a series of predisposing factors on the basis of chronic liver diseases, and it is characterized by multiple organ failure and high short-term mortality. The onset of systemic inflammation is one of the important influencing factors for the progression of ACLF and is the body's natural defense against infection; however, the excessive release of inflammatory mediators breaks the original dynamic balance between "pro-inflammation" and "anti-inflammation", which may aggravate liver function impairment and even lead to decompensation. Therefore, the intensity of inflammatory response is closely associated with the prognosis of patients with ACLF, while at present, not enough attention has been paid to the impact of inflammatory response on patients with ACLF and the measures to deal with cytokine storm. Therefore, this article summarizes the impact of inflammatory response on ACLF and related advances in treatment, so as to provide ideas for the diagnosis and treatment of ACLF in clinical practice.
-
Key words:
- Acute-On-Chronic Liver Failure /
- Inflammation /
- Therapeutics /
- Prognosis
-
[1] SARIN SK, CHOUDHURY A, SHARMA MK, et al. Correction to: 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(6): 826-828. DOI: 10.1007/s12072-019-09980-1. [2] BAJAJ JS, HEUMAN DM, HYLEMON PB, et al. Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis[J]. Aliment Pharmacol Ther, 2014, 39(10): 1113-1125. DOI: 10.1111/apt.12695. [3] 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. [4] TANG SH, ZENG WZ, JIANG MD, et al. Research progress in prediction of clinical outcome in patients with liver failure[J]. J Clin Hepatol, 2015, 31(1): 135-138. DOI: 10.3969/j.issn.1001-5256.2015.01.031.汤善宏, 曾维政, 蒋明德, 等. 肝衰竭患者临床预后判断研究进展[J]. 临床肝胆病杂志, 2015, 31(1): 135-138. DOI: 10.3969/j.issn.1001-5256.2015.01.031. [5] ALBILLOS A, de GOTTARDI A, RESCIGNO M. The gut-liver axis in liver disease: Pathophysiological basis for therapy[J]. J Hepatol, 2020, 72(3): 558-577. DOI: 10.1016/j.jhep.2019.10.003. [6] MICHELENA J, ALTAMIRANO J, ABRALDES JG, et al. Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis[J]. Hepatology, 2015, 62(3): 762-772. DOI: 10.1002/hep.27779. [7] CULLARO G, SHARMA R, TREBICKA J, et al. Precipitants of acute-on-chronic liver failure: an opportunity for preventative measures to improve outcomes[J]. Liver Transpl, 2020, 26(2): 283-293. DOI: 10.1002/lt.25678. [8] ZACCHERINI G, WEISS E, MOREAU R. Acute-on-chronic liver failure: Definitions, pathophysiology and principles of treatment[J]. JHEP Rep, 2021, 3(1): 100176. DOI: 10.1016/j.jhepr.2020.100176. [9] 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. [10] 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. [11] BAJAJ JS, VARGAS HE, REDDY KR, et al. Association between intestinal microbiota collected at hospital admission and outcomes of patients with cirrhosis[J]. Clin Gastroenterol Hepatol, 2019, 17(4): 756-765. e3. DOI: 10.1016/j.cgh.2018.07.022. [12] VILLANUEVA C, ALBILLOS A, GENESCÀ J, et al. Bacterial infections adversely influence the risk of decompensation and survival in compensated cirrhosis[J]. J Hepatol, 2021, 75(3): 589-599. DOI: 10.1016/j.jhep.2021.04.022. [13] PIANO S, SINGH V, CARACENI P, et al. Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide[J]. Gastroenterology, 2019, 156(5): 1368-1380. e10. DOI: 10.1053/j.gastro.2018.12.005. [14] 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. [15] FERNÁNDEZ J, ANGELI P, TREBICKA J, et al. Efficacy of albumin treatment for patients with cirrhosis and infections unrelated to spontaneous bacterial peritonitis[J]. Clin Gastroenterol Hepatol, 2020, 18(4): 963-973. e14. DOI: 10.1016/j.cgh.2019.07.055. [16] CARACENI P, RIGGIO O, ANGELI P, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): An open-label randomised trial[J]. Lancet, 2018, 391(10138): 2417-2429. DOI: 10.1016/S0140-6736(18)30840-7. [17] FERNÁNDEZ J, CLÀRIA J, AMORÓS A, et al. Effects of albumin treatment on systemic and portal hemodynamics and systemic inflammation in patients with decompensated cirrhosis[J]. Gastroenterology, 2019, 157(1): 149-162. DOI: 10.1053/j.gastro.2019.03.021. [18] GUSTOT T, JALAN R. Acute-on-chronic liver failure in patients with alcohol-related liver disease[J]. J Hepatol, 2019, 70(2): 319-327. DOI: 10.1016/j.jhep.2018.12.008. [19] ARROYO V, MOREAU R, JALAN R. Acute-on-chronic liver failure[J]. N Engl J Med, 2020, 382(22): 2137-2145. DOI: 10.1056/NEJMra1914900. [20] ZHANG YC, BI YZ, FANG X, et al. Protective effect of probiotics in rats with acute-on-chronic liver failure and related mechanism[J]. J Clin Hepatol, 2019, 35(7): 1570-1575. DOI: 10.3969/j.issn.1001-5256.2019.07.029.张永超, 毕研贞, 方萧, 等. 益生菌对慢加急性肝衰竭大鼠模型的保护作用及其机制[J]. 临床肝胆病杂志, 2019, 35(7): 1570-1575. DOI: 10.3969/j.issn.1001-5256.2019.07.029. [21] PHILIPS CA, PHADKE N, GANESAN K, et al. Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis[J]. Indian J Gastroenterol, 2018, 37(3): 215-225. DOI: 10.1007/s12664-018-0859-4. [22] MULLISH BH, MCDONALD J, THURSZ MR, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial[J]. Hepatology, 2017, 66(4): 1354-1355. DOI: 10.1002/hep.29369. [23] HARTMANN P, HOCHRATH K, HORVATH A, et al. Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice[J]. Hepatology, 2018, 67(6): 2150-2166. DOI: 10.1002/hep.29676. [24] GOEL A, RAHIM U, NGUYEN LH, et al. Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis[J]. Aliment Pharmacol Ther, 2017, 46(11-12): 1029-1036. DOI: 10.1111/apt.14361. [25] ACHARYA C, SAHINGUR SE, BAJAJ JS. Microbiota, cirrhosis, and the emerging oral-gut-liver axis[J]. JCI Insight, 2017, 2(19): e94416. DOI: 10.1172/jci.insight.94416. [26] FISCHER P, STEFANESCU H, HATEGAN R, et al. Bacterial infection-related acute-on-chronic liver failure: The standpoint matters![J]. J Hepatol, 2021, 75(4): 1009-1010. DOI: 10.1016/j.jhep.2021.04.046. [27] WU B, DU LY, MA YJ, et al. Effects of different combinations of artificial liver support system on efficacy and inflammatory indexes of patients with hepatitis B virus-related acute-on-chronic liver failure in early and middle stages[J/CD]. Chin J Liver Dis(Electr Version), 2021, 13(1): 32-38. DOI: 10.3969/j.issn.1674-7380.2021.01.006.吴蓓, 杜凌遥, 马元吉, 等. 不同组合人工肝支持系统治疗乙型肝炎病毒相关早、中期慢加急性肝衰竭患者的疗效及对炎症指标的影响[J/CD]. 中国肝脏病杂志(电子版), 2021, 13(1): 32-38. DOI: 10.3969/j.issn.1674-7380.2021.01.006. [28] GUO X, WU F, GUO W, et al. Comparison of plasma exchange, double plasma molecular adsorption system, and their combination in treating acute-on-chronic liver failure[J]. J Int Med Res, 2020, 48(6): 300060520932053. DOI: 10.1177/0300060520932053. [29] MAIWALL R, BAJPAI M, CHOUDHURY AK, et al. Therapeutic plasma-exchange improves systemic inflammation and survival in acute-on-chronic liver failure: A propensity-score matched study from AARC[J]. Liver Int, 2021, 41(5): 1083-1096. DOI: 10.1111/liv.14806. [30] SUNDARAM V, JALAN R, WU T, et al. Factors associated with survival of patients with severe acute-on-chronic liver failure before and after liver transplantation[J]. Gastroenterology, 2019, 156(5): 1381-1391. e3. DOI: 10.1053/j.gastro.2018.12.007. [31] KHANAM A, TREHANPATI N, RIESE P, et al. Blockade of neutrophil's chemokine receptors CXCR1/2 abrogate liver damage in acute-on-chronic liver failure[J]. Front Immunol, 2017, 8: 464. DOI: 10.3389/fimmu.2017.00464. [32] ANAND L, BIHARI C, KEDARISETTY CK, et al. Early cirrhosis and a preserved bone marrow niche favour regenerative response to growth factors in decompensated cirrhosis[J]. Liver Int, 2019, 39(1): 115-126. DOI: 10.1111/liv.13923. [33] ENGELMANN C, MARTINO VD, KERBERT A, et al. The current status of granulocyte-colony stimulating factor to treatacute-on-chronic liver failure[J]. Semin Liver Dis, 2021, 41(3): 298-307. DOI: 10.1055/s-0041-1723034. [34] LIN BL, CHEN JF, QIU WH, et al. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial[J]. Hepatology, 2017, 66(1): 209-219. DOI: 10.1002/hep.29189. [35] AHMAD A, WALI AF, REHMAN MU, et al. Therapeutic potential of rhododendron arboreum polysaccharides in an animal model of lipopolysaccharide-inflicted oxidative stress and systemic inflammation[J]. Molecules, 2020, 25(24): 6045. DOI: 10.3390/molecules25246045. [36] WANG X, SUN M, YANG X, et al. Value of liver regeneration in predicting short-term prognosis for patients with hepatitis B-related acute-on-chronic liver failure[J]. Biomed Res Int, 2020, 2020(4): 1-7. DOI: 10.1155/2020/5062873.
本文二维码
计量
- 文章访问数: 496
- HTML全文浏览量: 93
- PDF下载量: 76
- 被引次数: 0