Acute Liver Failure (ALF) Model

Model Description

Acute Liver Failure (ALF) is a rapidly progressive hepatic syndrome characterized by sudden hepatocyte necrosis, coagulopathy, and hepatic encephalopathy in previously healthy individuals. Our D-galactosamine (D-GalN)-induced ALF model in Bama minipigs meets the Terblanche & Hickman criteria for preclinical ALF studies, offering:

• Human-like pathophysiology: Mirrors viral-induced ALF in metabolic and histopathological profiles
• Controlled hepatotoxicity: Selective liver injury with minimal extrahepatic toxicity
• High reproducibility: 95% model success rate with defined 36-48h progression

Key Advantages:
✓ Large animal relevance: Anatomical/physiological similarity to humans
✓ Staged encephalopathy: Grade II+ neurological symptoms replicating clinical ALF
✓ Therapeutic window: Optimal for interventions (e.g., liver support systems, drug testing)

Applications

• Hepatoprotective drug evaluation (N-acetylcysteine, prostaglandin analogs)
• Bioartificial liver device testing
• Liver transplantation timing studies
• Coagulopathy management research

Modeling Protocol — D-GalN Induction Workflow

1. Pre-surgical Prep:

• Jugular vein catheterization under general anesthesia (isoflurane 2-3%)
• 36h postoperative recovery

2. D-GalN Administration:

• Dose: 1.5g/kg D-galactosamine hydrochloride (freshly prepared in saline)
• Route: Slow IV infusion via jugular catheter (30min duration)

3. Monitoring Phase:

• 36-48h: Track neurological status (hepatic encephalopathy grading)
• Humane endpoints: INR >3.0 ∙ Grade III encephalopathy

Validation & Testing

Technical Advantages