Subtyping of acute-on-chronic liver failure: Clinical value and breakthrough directions

Acute-on-chronic liver failure （ACLF） is an acute decompensation syndrome that develops on the background of chronic liver disease and is characterized by high mortality， rapid disease progression， complex clinical phenotypes， and a narrow window for reversibility. At present， there is still a lack of a unified standardized diagnostic system for ACLF globally， and there are significant differences between different diagnostic criteria in terms of liver failure， extrahepatic organ failure， and high-risk states within specific etiological contexts. To achieve individualized risk stratification of ACLF patients and optimize the allocation of clinical resources， it is urgently needed to establish a scientifically sound and precise classification system. Traditional static diagnostic models are confined only to baseline assessment and mortality prediction and fail to reflect dynamic disease evolution or effectively distinguish treatment response across different groups of patients. This article systematically reviews the major definitions and classification systems of ACLF at the current stage， analyzes the application value and limitations of various classification frameworks in clinical treatment decision-making， prognostic risk assessment， and clinical trial design， and proposes that the clinical classification system for ACLF should move beyond the single baseline evaluation approach toward a dynamic， treatment-oriented， and cross-etiology integrated assessment model， in order to provide a more precise theoretical basis for clinical diagnosis and treatment regarding artificial liver support， intensive care management， liver regeneration therapies， and determination of indications for liver transplantation.