Chapter 8 - Gut–liver–brain axis in chronic liver disease with a focus on hepatic encephalopathy

Abstract

Hepatic encephalopathy (HE) or brain dysfunction due to liver insufficiency and/or portosystemic shunting is one of the determinants of prognosis and outcome of liver cirrhosis. It is a key parameter in liver cirrhosis severity and organ transplantation scores. HE remains a clinical diagnosis, yet there are forms of HE, where mental or motor defect is usually not yet recognizable and specific tests need to be performed to assess this covert HE. Pathophysiologically, hyperammonemia remains the crucial factor in the pathogenesis of HE leading to astrocyte swelling and a glial edema which accounts for psychological and psychomotor abnormalities through impaired glioneuronal communication. The treatment of HE includes the management of triggering causes and the use of different therapeutic strategies of ammonia-scavenging in the gut and the circulation. Besides that, liver cirrhosis is associated with a chronic inflammatory milieu and recent works have established alterations of the gut microbiome that seem to be specific for HE patients in comparison to control populations and liver cirrhosis patients without overt HE. These are associated with distinct neuroimaging profiles of astroglial and neuronal injury. Therapeutically, strategies to target the gut microbiome via antibiotic treatment (rifaximine) or experimental therapies based on fecal microbiota transplantation have shown beneficial effects on HE and support the concept of microbiome-specific effects on HE in the sense of a gut–liver–brain axis.