Acute-on-chronic liver failure: from definitions to management

Acute-on-chronic liver failure (ACLF) represents a rapidly progressive deterioration in chronic liver disease (CLD) marked by multi-organ dysfunction and high short-term mortality. Although consensus on a single definition remains elusive, the clinical phenotype is increasingly recognized across diverse populations, with regional differences in underlying liver disease and precipitants influencing diagnostic criteria and reported incidence. Bacterial infections, alcohol-associated hepatitis (AH), viral hepatitis flares, and drug-induced liver injury (DILI) are among the most common intrahepatic and extrahepatic triggers. The pathophysiology of ACLF reflects immune dysregulation and circulatory collapse, leading to organ failure (OF). This complex interplay may vary according to the number and type of failing organs, the severity of the underlying liver disease, and the nature of the precipitating event. Short-term mortality in ACLF remains high and increases in proportion to the number of OFs. Therapeutic options remain largely supportive, as no disease-modifying therapies have yet been established clinical benefit. Emerging therapies, such as liver support systems, have yet to demonstrate a clear long-term survival advantage. Liver transplantation (LT) remains the sole curative option with demonstrated survival benefit in carefully selected candidates. Due to the high risk of mortality in ACLF, early engagement of palliative care (PC) alongside evaluation for transplant is essential. Early recognition and timely triage remain central to improving outcomes in this high-risk population. This review explores the definitions, prognosis and clinical course of ACLF, emphasizing the importance of early recognition and intervention.