Experimental models of hepatic encephalopathy: ISHEN guidelines

Roger F. Butterworth, Michael D. Norenberg, Vicente Felipo, Peter Ferenci, Jan Albrecht, Andres T. Blei

Research output: Contribution to journalReview articlepeer-review

219 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)783-788
Number of pages6
JournalLiver International
Issue number6
StatePublished - Jun 19 2009


  • Acute liver failure
  • Ammonia
  • Animal models
  • Astrocytes
  • Azoxymethane
  • Bile duct ligation
  • Cirrhosis
  • Galactosamine
  • Hepatic encephalopathy
  • Portacaval anastomosis
  • Thioacetamide

ASJC Scopus subject areas

  • Hepatology


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