ACUTE ON CHRONIC LIVER FAILURE: A SYSTEMATIC REVIEW

Acute on chronic liver failure (ACLF) is a clinical syndrome characterized by acute hepatic decompensation in patients with pre-existing chronic liver disease, often accompanied by systemic inflammation, multi-organ failure, and high short-term mortality. Despite increasing recognition, definitions remain heterogeneous across regions, and management strategies are limited, underscoring the need for harmonized frameworks and evidence-based interventions. A systematic search of PubMed, Scopus, Web of Science, and Embase was conducted for studies published between January 2010 and October 2025. Inclusion criteria encompassed original research, systematic reviews, meta-analyses, and guidelines addressing ACLF epidemiology, pathogenesis, diagnostic criteria, management, or outcomes in adults. Exclusion criteria included case reports, pediatric ACLF, non-English publications, and studies lacking standardized definitions. Study selection followed PRISMA 2020 guidelines, with risk of bias assessed using ROBINS-I and AMSTAR-2. Forty-eight studies met inclusion criteria. ACLF definitions varied, with the EASL-CLIF Consortium emphasizing organ failure scoring, while APASL focused on hepatic insult with jaundice and coagulopathy. Pathogenesis involved systemic inflammation, immune dysregulation, and gut dysbiosis, leading to multi-organ dysfunction. Mortality rates ranged from 40–70% within 90 days. Management strategies included supportive care, infection control, antivirals, artificial liver support systems, and liver transplantation. Transplantation remained the only definitive therapy, though patient selection and timing were critical. ACLF is a heterogeneous syndrome with high mortality. Harmonization of diagnostic criteria, early identification, and improved access to transplantation are essential. Future research should focus on immunomodulatory therapies, biomarker development, and equitable liver transplant policies to improve outcomes.