Fig. 1. Pathophysiology of HE.

Following the development of liver failure or decompensated liver cirrhosis, there is an increase of circulating bile acids, amino acids, serum ammonia, and toxic metabolites as well as an increase of systemic inflammation. The systemic elevation of these factors leads to an increase of their concentrations in the brain, leading to metabolic and oxidative stress as well as increased neuroinflammation. Elevation of circulating cytokines and chemokines is associated with increased activation of microglia in the brain and subsequent neuroinflammation. The increase of neuroinflammation as well as the metabolic and oxidative stress present under these conditions promote the development of HE.