慢加急性肝衰竭的疾病定义及发病机制

项晓刚; 尚大宝; 张金铭

doi:10.3969/j.issn.1001-5256.2023.10.003

慢加急性肝衰竭的疾病定义及发病机制

DOI: 10.3969/j.issn.1001-5256.2023.10.003

上海交通大学医学院附属瑞金医院感染科，肝脏疾病转化研究室，上海 200025

基金项目:

国家自然科学基金面上项目 (82170619);

国家自然科学基金面上项目 (81970544);

上海市优秀青年学术带头人计划 (20XD1422600);

上海市医苑新星杰出青年人才 (SHWJRS［2021］－99);

上海市人才发展基金 (2020097);

上海市临床重点专科建设项目 (shslczdzk01103)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：项晓刚撰写论文，尚大宝、张金铭审校文献。

详细信息

通信作者:
项晓刚， shine－xxg@163.com （ORCID： 0000－0003－0999－2950）

计量
- 文章访问数: 396
- HTML全文浏览量: 82
- PDF下载量: 138
- 被引次数: 0
出版历程
- 收稿日期: 2023-07-11
- 出版日期: 2023-10-30

The definition and pathogenesis of acute－on－chronic liver failure

Department of Infectious Diseases，Translational Laboratory of Liver Diseases，Ruijin Hospital，Shanghai Jiao Tong University School of Medicine，Shanghai 200025，China

Research funding:

National Natural Science Foundation of China (82170619);

National Natural Science Foundation of China (81970544);

Program for Young Outstanding Academic Leaders (20XD1422600);

Shanghai Rising Stars of Medical Talent Youth Development Program Outstanding Youth Medical Talents (SHWJRS［2021］－99);

Shanghai talent development fund (2020097);

Shanghai Municipal Key Clinical Specialty (shslczdzk01103)

More Information

Corresponding author: XIANG Xiaogang， shine－xxg@163.com （ORCID： 0000－0003－0999－2950）

摘要

摘要: 慢加急性肝衰竭（ACLF）的概念自提出后近三十年来，已经被各国学者广泛接受，但是关于ACLF的疾病定义和诊断在世界范围至今仍没有形成一套统一的标准。近年来，ACLF疾病描述中慢性肝病基础、肝内或肝外的急性损伤、急性肝功能失代偿、肝外器官功能衰竭、短期高病死率以及病程具有可逆性等关键特征，东西方已在逐渐缩小分歧中趋近共识。关于ACLF的发病机制目前尚未完全阐明，相关研究大多集中在全身炎症反应和免疫功能障碍方向。
- 慢加急性肝衰竭 /
- 病理过程 /
- 全身炎症反应综合征
Abstract: The concept of acute－on－chronic liver failure （ACLF） has been widely accepted by scholars around the world since it was proposed nearly 30 years ago， but there are still no uniform criteria for the definition and diagnosis of ACLF worldwide. In recent years， differences have been gradually narrowed and a consensus has been reached in the key features of the disease description for ACLF， such as the underlying chronic liver diseases， acute intrahepatic or extrahepatic injury， acute liver function decompensation， extrahepatic organ failure， high short－term mortality rates， and reversible course of the disease. The pathogenesis of ACLF remains unclear， and most studies focus on systemic inflammatory response and immune dysfunction.
- Acute－On－Chronic Liver Failure /
- Pathologic Processes /
- Systemic Inflammatory Response Syndrome

HTML全文

参考文献(45)

[1]	OHNISHI H, SUGIHARA J, MORIWAKI H, et al. Acute－on－chronic liver failure[J]. Ryoikibetsu Shokogun Shirizu, 1995, 7: 217－ 219.
[2]	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. Guidelines for diagnosis and treatment liver failure[J]. Inter J Epidemiol Infect Dis, 2006, 33( 4): 217－ 221. DOI: 10.3760/cma.j.issn.1673－4149.2006.04.001. 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. 肝衰竭诊疗指南[J]. 国际流行病学传染病学杂志, 2006, 33( 4): 217－ 221. DOI: 10.3760/cma.j.issn.1673－4149.2006.04.001.
[3]	SARIN SK, KUMAR A, ALMEIDA JA, et al. Acute－on－chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver(APASL)[J]. Hepatol Int, 2009, 3( 1): 269－ 282. DOI: 10.1007/s12072－008－9106－x.
[4]	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. Guidelines for diagnosis and treatment liver failure[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]	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.e 1－ 9. DOI: 10.1053/j.gastro.2013.02.042.
[6]	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.
[7]	SARIN SK, KEDARISETTY CK, ABBAS Z, et al. Acute－on－chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver(APASL) 2014[J]. Hepatol Int, 2014, 8( 4): 453－ 471. DOI: 10.1007/s12072－014－9580－2.
[8]	JALAN R, YURDAYDIN C, BAJAJ JS, et al. Toward an improved definition of acute－on－chronic liver failure[J]. Gastroenterology, 2014, 147( 1): 4－ 10. DOI: 10.1053/j.gastro.2014.05.005.
[9]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin 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.
[10]	WU T, LI J, SHAO L, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus－related acute－on－chronic liver failure[J]. Gut, 2018, 67( 12): 2181－ 2191. DOI: 10.1136/gutjnl－2017－314641.
[11]	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.
[12]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines on acute－on－chronic liver failure[J]. J Hepatol, 2023, 79( 2): 461－ 491. DOI: 10.1016/j.jhep.2023.04.021.
[13]	LUO J, LI J, LI P, et al. Acute－on－chronic liver failure: far to go－a review[J]. Crit Care, 2023, 27( 1): 259. DOI: 10.1186/s13054－023－04540－4.
[14]	MEZZANO G, JUANOLA A, CARDENAS A, et al. Global burden of disease: acute－on－chronic liver failure, a systematic review and meta－analysis[J]. Gut, 2022, 71( 1): 148－ 155. DOI: 10.1136/gutjnl－2020－322161.
[15]	NGU N, FLANAGAN E, BELL S, et al. Acute－on－chronic liver failure: Controversies and consensus[J]. World J Gastroenterol, 2023, 29( 2): 232－ 240. DOI: 10.3748/wjg.v29.i2.232.
[16]	MORRISON MA, ARTRU F, TROVATO FM, et al. Potential therapies for acute－on－chronic liver failure[J]. Liver Int, 2023. DOI: 10.1111/liv.15545.
[17]	van der MERWE S, CHOKSHI S, BERNSMEIER C, et al. The multifactorial mechanisms of bacterial infection in decompensated cirrhosis[J]. J Hepatol, 2021, 75( Suppl 1): S82－S100. DOI: 10.1016/j.jhep.2020.11.029.
[18]	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.
[19]	ZANETTO A, PELIZZARO F, CAMPELLO E, et al. Severity of systemic inflammation is the main predictor of ACLF and bleeding in individuals with acutely decompensated cirrhosis[J]. J Hepatol, 2023, 78( 2): 301－ 311. DOI: 10.1016/j.jhep.2022.09.005.
[20]	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.
[21]	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.
[22]	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.
[23]	ZACCHERINI G, AGUILAR F, CARACENI P, et al. Assessing the role of amino acids in systemic inflammation and organ failure in patients with ACLF[J]. J Hepatol, 2021, 74( 5): 1117－ 1131. DOI: 10.1016/j.jhep.2020.11.035.
[24]	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.
[25]	WEISS E, DE LA PEÑA－RAMIREZ C, AGUILAR F, et al. Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models(CLIF－C MET)[J]. Gut, 2023, 72( 8): 1581－ 1591. DOI: 10.1136/gutjnl－2022－328708.
[26]	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.
[27]	LANGE CM, MOREAU R. Immunodysfunction in acute－on－chronic liver failure[J]. Visc Med, 2018, 34( 4): 276－ 282. DOI: 10.1159/000488690.
[28]	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.
[29]	SAMUEL D. Systemic inflammation and liver cirrhosis complications: Driving or secondary event? How to square the circle?[J]. J Hepatol, 2021, 74( 3): 508－ 510. DOI: 10.1016/j.jhep.2021.01.001.
[30]	ENGELMANN C, ZHANG IW, CLÀRIA J. Mechanisms of immunity in acutely decompensated cirrhosis and acute－on－chronic liver failure[J]. Liver Int, 2023. DOI: 10.1111/liv.15644.
[31]	XIANG X, FENG D, HWANG S, et al. Interleukin－22 ameliorates acute－on－chronic liver failure by reprogramming impaired regeneration pathways in mice[J]. J Hepatol, 2020, 72( 4): 736－ 745. DOI: 10.1016/j.jhep.2019.11.013.
[32]	ZHAI H, ZHANG J, SHANG D, et al. The progress to establish optimal animal models for the study of acute－on－chronic liver failure[J]. Front Med(Lausanne), 2023, 10: 1087274. DOI: 10.3389/fmed.2023.1087274.
[33]	ENGELMANN C, MEHTA G, TACKE F. Regeneration in acute－on－chronic liver failure－the phantom lost its camouflage[J]. J Hepatol, 2020, 72( 4): 610－ 612. DOI: 10.1016/j.jhep.2020.01.003.
[34]	ZHANG Y, ZHANG X, HAN J, et al. Downregulated VISTA enhances Th17 differentiation and aggravates inflammation in patients with acute－on－chronic liver failure[J]. Hepatol Int, 2023, 17( 4): 1000－ 1015. DOI: 10.1007/s12072－023－10505－0.
[35]	HE L, CAI Q, LIANG X, et al. ETS2 alleviates acute－on－chronic liver failure by suppressing excessive inflammation[J]. J Med Virol, 2023, 95( 4): e28710. DOI: 10.1002/jmv.28710.
[36]	BERNSMEIER C, POP OT, SINGANAYAGAM A, et al. Patients with acute－on－chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK[J]. Gastroenterology, 2015, 148( 3): 603－ 615.e 14. DOI: 10.1053/j.gastro.2014.11.045.
[37]	BERNSMEIER C, TRIANTAFYLLOU E, BRENIG R, et al. CD14+ CD15－HLA－DR－myeloid－derived suppressor cells impair antimicrobial responses in patients with acute－on－chronic liver failure[J]. Gut, 2018, 67( 6): 1155－ 1167. DOI: 10.1136/gutjnl－2017－314184.
[38]	YAO J, JI Y, LIU T, et al. Single－cell RNA sequencing shows t－cell exhaustion landscape in the peripheral blood of patients with hepatitis B virus－associated acute－on－chronic liver failure[J]. Gut Liver, 2023. DOI: 10.5009/gnl220449.[ Online ahead of print]
[39]	SARIN SK, CHOUDHURY A. Acute－on－chronic liver failure: terminology, mechanisms and management[J]. Nat Rev Gastroenterol Hepatol, 2016, 13( 3): 131－ 149. DOI: 10.1038/nrgastro.2015.219.
[40]	DURAND F, ROUX O, WEISS E, et al. Acute－on－chronic liver failure: Where do we stand?[J]. Liver Int, 2021, 41( Suppl 1): 128－ 136. DOI: 10.1111/liv.14855.
[41]	BR VK, SARIN SK. Acute－on－chronic liver failure－terminology, mechanisms and management[J]. Clin Mol Hepatol, 2023, 29( 3): 670－ 689. DOI: 10.3350/cmh.2022.0103.
[42]	QIANG R, LIU XZ, XU JC. The immune pathogenesis of acute－on－chronic liver failure and the danger hypothesis[J]. Front Immunol, 2022, 13: 935160. DOI: 10.3389/fimmu.2022.935160.
[43]	KOU K, SUN X, TIAN G, et al. The mechanisms of systemic inflammatory and immunosuppressive acute－on－chronic liver failure and application prospect of single－cell sequencing[J]. J Immunol Res, 2022, 2022: 5091275. DOI: 10.1155/2022/5091275.
[44]	JALAN R, SUNDARAM V. A new model for identification of HBV－related pre－ACLF[J]. JHEP Rep, 2022, 4( 10): 100554. DOI: 10.1016/j.jhepr.2022.100554.
[45]	JALAN R, D’AMICO G, TREBICKA J, et al. New clinical and pathophysiological perspectives defining the trajectory of cirrhosis[J]. J Hepatol, 2021, 75( Suppl 1): S14－S26. DOI: 10.1016/j.jhep.2021.01.018.