Objectives of the International Society for
Hepatic Encephalopathy and
Nitrogen Metabolism Commission were to identify well-characterized animal models of
hepatic encephalopathy (HE) and to highlight areas of animal modelling of the disorder that are in need of development. Features essential to HE modelling were identified. The best-characterized animal models of HE in
acute liver failure, the so-called Type A HE, were found to be the hepatic devascularized rat and the rat with
thioacetamide-induced toxic liver injury. In case of
chronic liver failure, surgical models in the rat involving end-to-side
portacaval anastomosis or bile duct
ligation were considered to best model minimal/mild (Type B) HE. Unfortunately, at this time, there are no satisfactory animal models of Type C HE resulting from end-stage
alcoholic liver disease or viral
hepatitis, the most common aetiologies encountered in patients. The commission highlighted the urgent need for such models and of improved models of HE in
chronic liver failure in general as well as a need for models of post-transplant neuropsychiatric disorders. Studies of HE pathophysiology at the cellular and molecular level continue to benefit from in vitro and or ex vivo models involving brain slices or exposure of cultured cells (principally cultured astrocytes) to toxins such as
ammonia,
manganese and pro-inflammatory
cytokines. More attention could be paid in the future to in vitro models involving the neurovascular unit, microglia and neuronal co-cultures in relation to HE pathogenesis.