Neurological Consequences of Liver Disease: The Liver-Brain Axis

The liver serves as a key metabolic and inflammatory organ involved in maintaining homeostasis of different organs and systems. This includes ensuring proper functioning of the central nervous system through a liver-brain axis that has bi-directional communication via signaling mediators and direct neural pathways. Damage to, or disease of, the liver from various etiologies leads to a loss of hepatic function which then impacts cognitive, motor, and other neurological functions. Severity, type and duration of liver dysfunction can impact the brain in different ways via different metabolic and immune challenges. Some of the hepatic factors that impact the brain include ammonia, cytokines, and bile acids. These factors can induce more apparent neurological changes, such as hepatic encephalopathy, while others induce more subtle changes which typically fall outside of the classical characterization of hepatic encephalopathy. The aim of this review is to outline the current knowledge of the liver-brain axis in pathological states. Specific emphasis is placed on how loss of liver function leads to systemic metabolic and inflammatory challenges and their subsequent impacts on hepatic and neural pathology. In addition, specific hepatic pathologies most associated with disruptions of the liver-brain axis will be focused on for more detailed analysis.