In liver disease, a number of systemic pathogenic factors are responsible for the onset and progression of hepatic encephalopathy. A reduced capacity of the liver to clear gut-derived ammonia leads to an increase in blood ammonia and neurotoxicity. Portal-systemic shunting as well as a reduction in muscle quality and/or muscle mass loss further increase the risk of developing hyperammonemia. Systemic oxidative stress and inflammation together with hyperammonemia can trigger cognitive decline. These factors can cross the blood-brain barrier and affect the brain directly or alter the permeability and signaling across the blood-brain barrier. Long considered a reversible disorder, there is ample amount of evidence demonstrating that repeated episodes of overt HE can prompt neuronal cell injury/death leading to irreversibility. This chapter describes a patient who embarks on the continuum of HE, describing precipitating factors involved in the pathogenesis of cognitive decline.
