Uncovering the Hepatocyte CEBPA-ORM1 Axis: A Novel Regulatory Pathway and Biomarker in Alcohol-Associated Liver Disease

Highlights

• The transcription factor CEBPA is significantly downregulated in human alcohol-associated liver disease (ALD), correlating with disease progression.
• The hepatocyte-specific CEBPA-ORM1 axis functions as a endogenous restriction mechanism against alcohol-induced hepatic steatosis and injury.
• Orosomucoid 1 (ORM1) is a direct transcriptional target of CEBPA and acts as a protective hepatokine.
• Exogenous administration of recombinant ORM1 or AAV-mediated restoration of the axis reverses hepatic lipid accumulation in preclinical models.
• Serum ORM1 levels serve as a robust inverse biomarker for staging the severity of ALD in clinical cohorts.

Background