Pathogenesis of hepatic encephalopathy: new insights from neuroimaging and molecular studies.

Hepatic encephalopathy (HE) is a major neuropsychiatric complication of both acute and chronic liver failure. Symptoms of HE include attentional deficits, alterations of sleep patterns and muscular incoordination progressing to stupor and coma. HE in acute liver failure may include seizures. Despite several decades of intensive scientific research, the precise causes of HE are still unknown. Attention has been focussed on two major areas, namely the role of blood-borne neurotoxins (particularly ammonia [1]) and the key role of the astrocyte [2]. One impediment in the search for pathophysiologic mechanisms in HE has resulted from the lack of standardization of terminology used to define the syndrome, both clinically and experimentally. Terms such as ‘chronic HE’ were commonly used to describe HE in chronic liver failure and it was frequently unclear whether ‘acute HE’ referred to acute liver failure or to acute decompensation in a patient with chronic liver failure. Fortunately, the year 2002 saw the publication of the final report [3] of a working party whose task was to better define HE from the standpoint of the standardization of clinical diagnosis. It was concluded that “HE reflects a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease. A multiaxial definition of HE is required that defines both the type of hepatic abnormality and the duration/characteristics of neurologic manifestations in chronic liver disease”. Three types of hepatic abnormality were defined, namely: