Hepatic encephalopathy

Abstract

Hepatic Encephalopathy (HE) refers to a wide spectrum of neurological and psychiatric alterations that may occur in patients with liver disease. Liver failure leads to the accumulation in brain of neurotoxic substances that are normally metabolized and eliminated by hepatic or biliary routes. Two neurotoxic substances have been identified in liver failure, ammonia and manganese. While it is generally held that ammonia plays a key role, the pathogenic mechanisms involved in HE still remain to be defined. Minimal HE (MHE) is an early and subclinical state of HE. MHE induced by the portal vein stricture was associated with moderated hyperammonemia and increased manganese levels related with a marked increase in portal blood pressure, as well as histopathological changes in astrocytes, cortical neurons and capillary vessels. Neurotoxins present in MHE, probably are involved in the cytoskeletal alterations observed in this MHE model, and they may affect the structural and functional neuronalastrocytic relationship. These could be mediated by the Hypoxia Induced Factor 1 stabilization resulting in a focal hypoxic tissue state. There is now a substantial body of research that strongly suggests whether ammonia and/or manganese induce these alterations showing a new pathway in MHE pathogenesis.