LIVER: Edited by Don C. RockeyAcute-on-chronic liver failure: update on pathogenesis, therapeutic targets, predictive models, and liver transplantationShah, Shivania; Goldberg, David S.bAuthor Information aDepartment of Medicine, University of Miami Miller School of Medicine bDivision of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA Correspondence to David S. Goldberg, MD, MSCE, Department of Medicine, University of Miami Miller School of Medicine, 1120 NW 14th Street, Room 807, Miami, Florida 33136, USA. Tel: +305 243 7956; e-mail: [email protected] Current Opinion in Gastroenterology: May 2021 - Volume 37 - Issue 3 - p 173-178 doi: 10.1097/MOG.0000000000000722 Buy Metrics Abstract Purpose of review Acute-on-chronic liver failure (ACLF) is a clinical syndrome in patients with chronic liver disease that is associated with multiple organ failures and a high short-term mortality. Systemic inflammation is suggested to play a key role in its pathogenesis, although the precise causative mechanism is unknown. The purpose of this review is to present and discuss new findings related to: mechanisms underlying ACLF, therapeutic targets, risk prediction models for developing ACLF, and liver transplantation for ACLF. Recent findings Recent studies of ACLF pathophysiology classified the immunosuppressive phenotype in monocytes. Investigation of therapeutic strategies identified inhibition of toll-like receptor-4 (TLR-4) and glutamine synthetase (GLUL) as potential targets. Recent studies identified novel risk prediction models for developing ACLF and enhanced our understanding of liver transplantation for ACLF to guide clinicians in determining that patients will benefit from transplantation. Summary Improved knowledge on the pathogenesis of ACLF and identification of TLR-4 and GLUL may lead to clinical trials to study the efficacy of these novel therapeutic targets for patients with ACLF. Liver transplantation is the only current treatment for ACLF. Given the limited availability of donor organs, recent studies have identified ACLF patients who may merit the highest waitlist priority. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.