Experimental models of hepatic encephalopathy: ISHEN guidelines

Area of Science:

• Neuroscience
• Hepatology
• Animal Modeling

Background:

• Hepatic encephalopathy (HE) is a complex neurological complication of liver dysfunction.
• Accurate animal models are crucial for understanding HE pathogenesis and developing treatments.
• Existing models primarily address acute liver failure (Type A HE) and minimal/mild chronic liver failure (Type B HE).

Framework:

• The International Society for Hepatic Encephalopathy and Nitrogen Metabolism Commission evaluated existing animal models of HE.
• Key features essential for effective HE modeling were identified.
• Models were assessed based on their ability to replicate different types and stages of HE.

Implementation:

• Well-characterized models for Type A HE include the hepatic devascularized rat and thioacetamide-induced liver injury rat.
• For Type B HE in chronic liver failure, surgical rat models like end-to-side portacaval anastomosis and bile duct ligation are considered suitable.
• Current limitations exist, particularly for modeling Type C HE associated with end-stage alcoholic or viral hepatitis.

Implications:

• There is an urgent need for improved animal models, especially for Type C HE and general chronic liver failure.
• Development of models for post-transplant neuropsychiatric disorders is also required.
• In vitro and ex vivo models using cell cultures and brain slices are valuable for studying HE at cellular and molecular levels, with potential for future advancements in neurovascular unit and co-culture models.