Acute-on-chronic liver failure: From definition to pathogenesis and therapy.

Area of Science:

• Hepatology
• Immunology
• Gastroenterology

Background:

• Acute-on-chronic liver failure (ACLF) is a recognized clinical entity but lacks universal diagnostic criteria.
• Despite widespread acceptance, global consensus on ACLF definition and diagnosis remains elusive.
• Key features like underlying chronic liver disease, acute insults, and organ failure are converging towards a consensus.

Purpose of the Study:

• To review the evolution of ACLF clinical definitions and propose clear diagnostic criteria.
• To summarize current understanding of ACLF pathogenesis, focusing on inflammation and immune dysfunction.
• To highlight novel therapeutic targets and introduce a new experimental mouse model for ACLF therapy assessment.

Main Methods:

• Literature review on ACLF definition evolution and diagnostic criteria.
• Synthesis of current research on ACLF pathogenesis, including systemic inflammation and immune response.
• Description of a novel experimental mouse model for evaluating potential ACLF therapies.

Main Results:

• Progress has been made in defining ACLF, narrowing differences in key clinical features.
• Systemic inflammation and immune dysfunction are identified as central to ACLF pathogenesis.
• A new mouse model offers a platform for preclinical assessment of ACLF treatments.

Conclusions:

• Clear diagnostic criteria for ACLF are proposed to facilitate global standardization.
• Understanding ACLF pathogenesis is crucial for developing effective therapies.
• The novel mouse model represents a significant advancement for ACLF therapeutic research.