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

• Published in: Journal of hepatology Vol. 75; no. Suppl 1; pp. S49 - S66
• Main Authors: Engelmann, Cornelius, Clària, Joan, Szabo, Gyongyi, Bosch, Jaume, Bernardi, Mauro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2021
• Subjects: ACLF; Acute-on-chronic liver failure; Acute-On-Chronic Liver Failure - diagnosis; Acute-On-Chronic Liver Failure - etiology; Ascites; Cirrhosis; DAMP; Hepatic encephalopathy; Humans; Inflammation; Liver Circulation; Liver Cirrhosis - complications; Liver Cirrhosis - immunology; Liver Cirrhosis - metabolism; Liver Cirrhosis - physiopathology; Organ failure; Oxidative Stress; PAMP; Prognosis; Tissue injury; Variceal bleeding; Organ failure; Cirrhosis; PAMP; ACLF; Tissue injury; Variceal bleeding; Acute-on-chronic liver failure; Ascites; Hepatic encephalopathy; DAMP
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2021.01.002

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.