Hepatic encephalopathy: Lessons from preclinical studies

Abstract

Hepatic encephalopathy (HE) is a major complication that is closely related to the progression of end-stage liver disease. Metabolic changes in advanced liver failure can promote cognition impairment, attention deficits and motor dysfunction that may result in coma and death. HE can be subdivided according to the type of hepatic injury, namely, type A, which results from acute liver failure, type B, which is associated with a portosystemic shunting without intrinsic liver disease, and type C, which is due to chronic liver disease. Several studies have investigated the pathogenesis of the disease, and most of the mechanisms have been explored using animal models. This article aimed to review the use of preclinical models to investigate HE. The most used animal species are rats and mice. Experimental models of type A HE include surgical procedures and the administration of hepatotoxic medications, whereas models of types B and C HE are generally surgically induced lesions in liver tissue, which evolve to hepatic cirrhosis. Preclinical models have allowed the comprehension of the pathways related to HE.

Keywords: Acute liver failure; Hepatic cirrhosis; Hepatic encephalopathy; Hyperammonemia; Neuroinflammation; Preclinical studies.

Figure 1

Main pathophysiological feature of the available models of hepatic encephalopathy. APAP: Acetaminophen; A/C Hamm: Acute/chronic hyperammonemia; BDL: Bile duct-ligated; CCl4: Carbon tetrachloride; GP-VS: Graded portal-vein stenosis; PCA: Portosystemic anastomosis; TAA: Thioacetamide.