2021 ISHEN guidelines on animal models of hepatic encephalopathy

Abstract

This working group of the International Society of Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) was commissioned to summarize and update current efforts in the development and characterization of animal models of hepatic encephalopathy (HE). As defined in humans, HE in animal models is based on the underlying degree and severity of liver pathology. Although hyperammonemia remains the key focus in the pathogenesis of HE, other factors associated with HE have been identified, together with recommended animal models, to help explore the pathogenesis and pathophysiological mechanisms of HE. While numerous methods to induce liver failure and disease exist, less have been characterized with neurological and neurobehavioural impairments. Moreover, there still remains a paucity of adequate animal models of Type C HE induced by alcohol, viruses and non-alcoholic fatty liver disease; the most common etiologies of chronic liver disease.

Keywords: acute liver failure; behaviour; bile duct ligation; chronic liver disease; hepatic encephalopathy; hyperammonemia; liver toxins; neurological deficits; portocaval anastomosis.

Figure 1:. Common methods for the induction of liver failure/disease

Various ways of inducing acute liver failure or chronic liver disease. Red boxes; surgical methods, grey boxes; toxin approaches.

Figure 2:

Advantages and disadvantages of working with different experimental animals.

Figure 3:. Behavioral tests for investigating HE in rodents

Various and numerous tests or methods are available to evaluate cognitive impairment, sensory-motor deficits as well as anxiety and depression.

Figure 4:. Recommendations for Type A, B and C HE animal models

The practicality, reproducibility and recommendations for the different animal models of type A, B and C HE. *** Excellent, ** Moderate * Poor.