Acute-on-chronic liver failure: definition, prognosis and management

Abstract

Acute-on-chronic liver failure (ACLF) is a recently described entity in chronic liver disease defined by acute hepatic decompensation, organ failure and a high risk of short-term mortality (usually less than 4 weeks). This condition is distinct from acute liver failure and stable progression of cirrhosis in numerous ways, including triggering precipitant factors, systemic inflammation, rapid progression and a potential for recovery. While a clear definition of ACLF has been forwarded from a large European Consortium study, some heterogeneity remains in how patients present and the types of organ failure, depending on whether they are described in Asian or European studies. Active alcoholism, acute alcoholic hepatitis and infections are the most frequent precipitants for ACLF. Underpinning the pathophysiology of ACLF is a state of persistent inflammation and immune dysfunction, collectively driving a systematic inflammatory response syndrome and an increased propensity to sepsis. Prevention and early treatment of organ failure are key in influencing survival. Given increasing organ shortage and more marginal grafts, liver transplantation is a limited resource and emphasises the need for new therapies to improve ACLF outcomes. Recent data indicate that liver transplantation has encouraging outcomes even in patients with advanced ACLF if patients are carefully selected during the permissive window of clinical presentation. ACLF remains a significant challenge in the field of hepatology, with considerable research and resource being channelled to improve upon the definition, prognostication, treatment and unravelling of mechanistic drivers. This Review discusses updates in ACLF definition, prognosis and management.

Inflammatory Signature in Acute-on-Chronic Liver Failure Includes Increased Expression of Neutrophil Specific Genes ELANE, MPO and CD177 Running Title: Neutrophil Transcriptomics in ACLF

“…This complicates studies on the pathogenesis of ACLF due the involvement of different kinds of PAMPS and DAMPS, interaction of different molecular and physiological processes 37 . Therefore, it is di cult to extrapolate ndings from one study to another and this has been a major challenge in ACLF biomarker research 38,39 . However, our observations which are made in an Indian cohort are corroborated by published studies carried out on genetically non-identical French population, particularly in the context of overexpression of neutrophil CD177 10 .…”

Acute-on-chronic liver failure: Controversies and consensus

“…Lack of a consensus remains problematic with the potential for delayed or missed diagnoses, and challenges in applying evidence-based treatment. There is clinical consensus that ACLF is a distinct syndrome to acute hepatic decompensation, however, patients may initially present with clinical features of a decompensating event including worsening of abdominal ascites, jaundice, gastrointestinal bleeding and hepatic encephalopathy (HE)[ 30 ]. Features of bacterial infection, such as urinary tract infection, pneumonia, or spontaneous bacterial peritonitis, with may also be present[ 5 ].…”

“…The APASL ACLF Research Consortium (AARC) ACLF score is a prognostic model constructed from the AARC database. It incorporates five variables, including lactate, grade of HE, INR, bilirubin and serum creatinine levels[ 37 ] to stratify patients into grade 1 (score of 5-7), grade 2 (score of 8-10) or grade 3 ACLF (score of 11-15), with 28 day mortality rates of 12.7%, 44.5%, and 85.9% respectively[ 30 ]. Grade I ACLF are said to have potential recovery, grade II require intensive monitoring and grade III need immediate intervention and consideration of transplantation[ 30 ].…”

Quantitative Plasma Proteomics Identifies Metallothioneins as a Marker of Acute-on-Chronic Liver Failure Associated Acute Kidney Injury

“…Acute-on-Chronic Liver Failure (ACLF) is a complex liver disease with a very high short-term mortality of ∼50% 1,2 . The hallmarks of ACLF are- systemic inflammation, innate immune dysfunction and extra-hepatic multiple organ failure (MOF) 3, 4 .…”