Immunopathogenesis of acute on chronic liver failure

Acute-on-chronic liver failure is a well-established description of a high mortality syndrome of chronic liver disease (usually cirrhosis) with organ failure. While the exact definition is under refinement the accepted understanding of this entity is in patients with chronic liver disease who have various organs in failure and where systemic inflammation is a major component of the pathobiology. There are limited therapies for a disease with such a poor prognosis and while improvements in the critical care management and for very few patients, liver transplantation, mean 50% can survive to hospital discharge, rapid application of new therapies is required. Here we explain the current understanding of the immunological abnormalities seen in ACLF across the innate and adaptive immune systems, the role of the hepatic cell death and the gut liver axis and recommendations for future research and treatment paradigms.