Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction

被引:263
作者
Engelmann, Cornelius [1 ,2 ,3 ,4 ]
Claria, Joan [5 ,6 ,7 ,8 ,9 ]
Szabo, Gyongyi [10 ]
Bosch, Jaume [11 ,12 ,13 ]
Bernardi, Mauro [14 ]
机构
[1] Charite Univ Med Berlin, Dept Hepatol & Gastroenterol, Augustenburger Pl 1, D-13353 Berlin, Germany
[2] UCL, Inst Liver & Digest Hlth, London, England
[3] Univ Hosp Leipzig, Sect Hepatol, Clin Gastroenterol & Rheumatol, Leipzig, Germany
[4] Berlin Inst Hlth BIH, Berlin, Germany
[5] European Fdn Study Chron Liver Failure EF Clif, Barcelona, Spain
[6] Grifols Chair, Barcelona, Spain
[7] Hosp Clin IDIBAPS, Biochem & Mol Genet Serv, Madrid, Spain
[8] CIBERehd, Madrid, Spain
[9] Univ Barcelona, Dept Biomed Sci, Barcelona, Spain
[10] Harvard Med Sch, Dept Med, Div Gastroenterol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA
[11] Univ Barcelona, IDIBAPS, Barcelona, Spain
[12] Univ Barcelona, CIBERehd, Barcelona, Spain
[13] Bern Univ, Dept Biomed Res DBMR, Bern, Switzerland
[14] Alma Mater Studiorum Univ Bologna, Dept Med & Surg Sci, Bologna, Italy
基金
欧盟地平线“2020”;
关键词
Cirrhosis; Acute-on-chronic liver failure; ACLF; Tissue injury; PAMP; DAMP; Ascites; Variceal bleeding; Hepatic encephalopathy; Organ failure; CHRONIC LIVER-FAILURE; ACUTE KIDNEY INJURY; INTERORGAN AMMONIA METABOLISM; ENDOTHELIAL GROWTH-FACTOR; VENOUS-PRESSURE GRADIENT; HYPERDYNAMIC CIRCULATION; NITRIC-OXIDE; MICROCIRCULATORY DYSFUNCTION; CLINICAL DECOMPENSATION; HEPATIC-ENCEPHALOPATHY;
D O I
10.1016/j.jhep.2021.01.002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acute-on-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure(s). The pathomechanisms involved in decompensation and disease progression are still not well understood, and as specific disease-modifying treatments do not exist, research to identify novel therapeutic targets is of the utmost importance. This review amalgamates the latest knowledge on disease mechanisms that lead to tissue injury and extrahepatic organ failure - such as systemic inflammation, mitochondrial dysfunction, oxidative stress and metabolic changes - and marries these with the classical paradigms of acute decompensation to form a single paradigm. With this detailed breakdown of pathomechanisms, we identify areas for future research. Novel disease-modifying strategies that break the vicious cycle are urgently required to improve patient outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:S49 / S66
页数:18
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