Hepatic encephalopathy (HE) defines a frequent neuropsychiatric manifestation of chronic and acute liver disease with disturbances of psychomotoric, intellectual, cognitive, emotional/affective, behavioural and fine motor functions of varying severity (for review see ref. 1). The syndrome is frequent and, depending on the population under study, 20-80% of cirrhotics may suffer from subclinical or manifest HE.It is a long-standing clinical experience that cirrhotic patients are prone to episodes of HE in response to sepsis or infections. Several mechanisms may underlie this observation. First, infections are associated with a protein catabolic state, which increases the ammonia load to the liver and impairs ammonia detoxication in muscle. Second, lipopolysaccharide (LPS) injection, which is frequently used as a sepsis model in the rat, induces an inactivating tyrosine nitration of hepatic glutamine synthetase with impairment of hepatic ammonia detoxication. Third, inflammatory cytokines, such as tumour necrosis factor (TNF)-alpha can act directly on the brain and trigger pathophysiological events leading to HE.
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