慢加急性肝衰竭的发病机制和治疗进展

尚大宝; 项晓刚

doi:10.3969/j.issn.1001-5256.2021.04.005

慢加急性肝衰竭的发病机制和治疗进展

DOI: 10.3969/j.issn.1001-5256.2021.04.005

尚大宝,
项晓刚^,

上海交通大学医学院附属瑞金医院感染科，上海 200025

基金项目:

国家自然科学基金面上项目 (81970544);

上海市青年优秀学术带头人计划 (20XD1422600);

上海市教委高峰高原学科建设计划 (20172008)

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：尚大宝参与文献检索和论文撰写；项晓刚参与课题思路的确定和论文修改。

详细信息

作者简介:
尚大宝(1995—)，男，主要从事慢加急性肝衰竭临床与发病机制方面的研究

通信作者:
项晓刚，shine-xxg@163.com

中图分类号: R575.3
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- 被引次数: 0
出版历程
- 收稿日期: 2021-01-07
- 录用日期: 2021-03-02
- 出版日期: 2021-04-20

Advances in the pathogenesis and treatment of acute-on-chronic liver failure

Dabao SHANG,
Xiaogang XIANG^,

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

摘要

摘要: 慢加急性肝衰竭(ACLF)是一类在慢性肝病基础上发生的以急性肝功能失代偿、肝外器官损伤和高短期死亡率为主要临床特征的严重临床综合征。欧美国家慢性肝病基础疾病以酒精性肝炎和慢性丙型肝炎为主，而我国及亚太地区以慢性乙型肝炎为主。尽管东西方肝脏基础疾病存在差异，但大多数ACLF患者发病的共同病理基础通常以长期慢性肝损伤导致的肝纤维化或肝硬化为主。目前，关于ACLF的研究正在世界各地广泛开展，但由于地域、患病人群及疾病诱因等多方面的差异，在ACLF定义、诊断标准及疾病管理等方面始终没有达成东西方共识。旨在从ACLF的定义、发病机制和疾病管理等方面展开阐述，以期为临床工作者提供能改善患者预后的新治疗策略。
- 慢加急性肝功能衰竭 /
- 病理过程 /
- 治疗学
Abstract: Acute-on-chronic liver failure (ACLF) is a type of severe clinical syndrome which occurs on the basis of chronic liver diseases and has the main clinical features of acute liver decompensation, extrahepatic organ damage, and high short-term mortality rate. The underlying diseases of chronic liver diseases are mainly alcoholic hepatitis and chronic hepatitis C in Western countries, while chronic hepatitis B is the main underlying disease of chronic liver diseases in China and the Asia-Pacific region. Although there are differences in underlying liver diseases between the East and the West, the common pathological basis of most ACLF patients is usually liver fibrosis or cirrhosis caused by long-term chronic liver injury. At present, the research on ACLF has been widely carried out all over the world; however, due to the differences in region, population, and disease triggers, no consensus has been reached on the definition, diagnostic criteria, and disease management of ACLF between the East and the West. This article elaborates on the definition, pathogenesis, and management of ACLF, in order to provide clinicians with new therapeutic strategies that would improve the prognosis of ACLF.
- Acute-On-Chronic Liver Failure /
- Pathologic Processes /
- Therapeutics

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表 1 评价ACLF中使用ECLS的研究

研究 (第一作者及年份)	试验设计	样本数 (例)	ECLS类型	生化功能改善	血流动力学改善	肝性脑病改善	生存率改善 ECLS vs SMT
Hassanein 2007^[17]	RCT(8个中心)	70	MARS	是	未测	是	未测
Kribben 2012^[18]	RCT(10个中心)	143	Prometheus	是	未测	未测	否(66% vs 63% 28 d)
Bañares 2013^[19]	RCT(19个中心)	189	MARS	是	未测	未测	否(60.7% vs 58.9% 28 d)
Yao 2019^[20]	非RCT(1个中心)	54	PE+DPMAS	是	未测	未测	是(57.4% vs 41.7% 28 d)

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参考文献(29)

[1]	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. Diagnostic and treatment guidelines for 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.
[2]	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.
[3]	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.
[4]	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.
[5]	JALAN R, STADLBAUER V, SEN S, et al. Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: A prospective cohort study[J]. Crit Care, 2012, 16(6): R227. DOI: 10.1186/cc11882.
[6]	SHI Y, YANG Y, HU Y, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults[J]. Hepatology, 2015, 62(1): 232-242. DOI: 10.1002/hep.27795.
[7]	HERNAEZ R, SOLÀ E, MOREAU R, et al. Acute-on-chronic liver failure: An update[J]. Gut, 2017, 66(3): 541-553. DOI: 10.1136/gutjnl-2016-312670.
[8]	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.
[9]	GARG V, GARG H, KHAN A, et al. Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure[J]. Gastroenterology, 2012, 142(3): 505-512.e1. DOI: 10.1053/j.gastro.2011.11.027.
[10]	CLÀRIA J, ARROYO V, MOREAU R. The acute-on-chronic liver failure syndrome, or when the innate immune system goes astray[J]. J Immunol, 2016, 197(10): 3755-3761. DOI: 10.4049/jimmunol.1600818.
[11]	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.
[12]	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, 2019, 3(1): 269-282. DOI: 10.1007/s12072-008-9106-x.
[13]	WANG J, MA K, HAN M, et al. Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic liver failure: Validation of the TPPM model[J]. Hepatol Int, 2014, 8(1): 64-71. DOI: 10.1007/s12072-013-9485-5.
[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]	THURSZ MR, RICHARDSON P, ALLISON M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis[J]. N Engl J Med, 2015, 372(17): 1619-1628. DOI: 10.1056/NEJMoa1412278.
[16]	SERSTÉ T, CORNILLIE A, NJIMI H, et al. The prognostic value of acute-on-chronic liver failure during the course of severe alcoholic hepatitis[J]. J Hepatol, 2018, 69(2): 318-324. DOI: 10.1016/j.jhep.2018.02.022.
[17]	HASSANEIN TI, TOFTENG F, BROWN RS Jr, et al. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis[J]. Hepatology, 2007, 46(6): 1853-1862. DOI: 10.1002/hep.21930.
[18]	KRIBBEN A, GERKEN G, HAAG S, et al. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure[J]. Gastroenterology, 2012, 142(4): 782-789.e3. DOI: 10.1053/j.gastro.2011.12.056.
[19]	BAÑARES R, NEVENS F, LARSEN FS, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial[J]. Hepatology, 2013, 57(3): 1153-1162. DOI: 10.1002/hep.26185.
[20]	YAO J, LI S, ZHOU L, et al. Therapeutic effect of double plasma molecular adsorption system and sequential half-dose plasma exchange in patients with HBV-related acute-on-chronic liver failure[J]. J Clin Apher, 2019, 34(4): 392-398. DOI: 10.1002/jca.21690.
[21]	SHEN Y, WANG XL, WANG B, et al. Survival benefits with artificial liver support system for acute-on-chronic liver failure: A time series-based meta-analysis[J]. Medicine (Baltimore), 2016, 95(3): e2506. DOI: 10.1097/MD.0000000000002506.
[22]	PIANO S, SCHMIDT HH, ARIZA X, et al. Association between grade of acute on chronic liver failure and response to terlipressin and albumin in patients with hepatorenal syndrome[J]. Clin Gastroenterol Hepatol, 2018, 16(11): 1792-1800.e3. DOI: 10.1016/j.cgh.2018.01.035.
[23]	THULUVATH PJ, THULUVATH AJ, HANISH S, et al. Liver transplantation in patients with multiple organ failures: Feasibility and outcomes[J]. J Hepatol, 2018, 69(5): 1047-1056. DOI: 10.1016/j.jhep.2018.07.007.
[24]	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.
[25]	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.
[26]	SAHA BK, MAHTAB MA, AKBAR S, et al. Therapeutic implications of granulocyte colony stimulating factor in patients with acute- on-chronic liver failure: Increased survival and containment of liver damage[J]. Hepatol Int, 2017, 11(6): 540-546. DOI: 10.1007/s12072-017-9814-1.
[27]	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.
[28]	XIANG X, HWANG S, FENG D, et al. Interleukin-22 in alcoholic hepatitis and beyond[J]. Hepatol Int, 2020, 14(5): 667-676. DOI: 10.1007/s12072-020-10082-6.
[29]	ARAB JP, SEHRAWAT TS, SIMONETTO DA, et al. An open-label, dose-escalation study to assess the safety and efficacy of IL-22 agonist F-652 in patients with alcohol-associated hepatitis[J]. Hepatology, 2020, 72(2): 441-453. DOI: 10.1002/hep.31046.