Experimental models for hepatic encephalopathy

Abstract

Although there are many models for animal testing, the ideal model for chronic liver disease involving hepatic encephalopathy has not been described yet. Different problems associated with the models have led researchers to develop their own, sometimes unique experimental models, which makes difficult the comparison between the results of the conducted studies (1). Hepatic encephalopathy (HE) definition, nomenclature, diagnosis and quantification consensus were published in 2002 (2) where three types of HE were considered: type A, associated with acute liver failure, type B, associated with the existence of porto-systemic communication (by-pass) without intrinsic liver disease and type C, associated to liver cirrhosis. HE type C, in turn, is classified according to their form of presentation as spontaneous or episodic HE, in relation to precipitating factors, persistent HE is subdivided into mild (HE grade I), severe (HE II-IV) or treatment-dependent (early developed after abolition of treatment) and finally, the minimal HE, as the first manifestation of HE. HE type C is the most common form and from a clinical point of view, the episodic HE type because of liver cirrhosis decompensation is the most typical and relevant. The ideal model of HE should reproduce most of the clinical features of this syndrome in humans, as occurring mainly in patients with chronic liver disease, being precipitated by defined factors, it should be reversible with the correction of precipitating factors and improved using rifaximin or ammonia lowering-drugs, being strongly associated with altered nitrogen metabolism and showing a wide spectrum of severity. Because most patients with HE also suffer from chronic liver disease, porto-systemic shunts, developed hyperammonemia and systemic inflammation it is highly desirable that animal models would include these facts (Fig. 1).