Role of circulating neurotoxins in the pathogenesis of hepatic encephalopathy: potential for improvement following their removal by liver assist devices

@article{Butterworth2003RoleOC,
  title={Role of circulating neurotoxins in the pathogenesis of hepatic encephalopathy: potential for improvement following their removal by liver assist devices},
  author={Roger F. Butterworth},
  journal={Liver International},
  year={2003},
  volume={23}
}
  • R. Butterworth
  • Published 1 June 2003
  • Biology, Medicine
  • Liver International
Abstract Both acute and chronic liver failure result in impaired cerebral function known as hepatic encephalopathy (HE). Evidence suggests that HE is the consequence of the accumulation in brain of neurotoxic and/or neuroactive substance including ammonia, manganese, aromatic amino acids, mercaptans, phenols, short‐chain fatty acids, bilirubin and a variety of neuroactive medications prescribed as sedatives to patients with liver failure. Brain ammonia concentrations may attain levels in excess… 
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References

SHOWING 1-10 OF 34 REFERENCES
Ammonia: key factor in the pathogenesis of hepatic encephalopathy.
TLDR
Cerebrospinal fluid and brain glutamine are found to be significantly elevated in cirrhotic patients with encephalopathy and in rats following portocaval anastomosis and in both cases, glutamine is finding to be elevated in a region-dependent manner.
Amino acid changes in regions of the CNS in relation to function in experimental portal-systemic encephalopathy
TLDR
Onset of severe neurological dysfunction was accompanied by significantly decreased glutamine and glutamate in striatum and cerebellum, results in region-selective effects with respect to glutamine-glutamate metabolism in the CNS.
Effect of Ammonia on Brain Serotonin Metabolism in Relation to Function in the Portacaval Shunted Rat
TLDR
Increased 5‐HIAA/5‐HT ratios after PCA and NH4Ac loading is demonstrated, suggesting increased 5‐HT turnover in the brains of shunted rats, but these changes do not appear to be related to the precipitation of coma as no significant difference in 5-HT turnover was observed between precoma and coma stages of HE.
Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts.
TLDR
The findings indicate that cerebral dysfunction in chronic, relapsing ammonia intoxication is not due to primary energy failure, and is suggested that ammonia-induced depletion of glutamic and aspartic acids, and inhibition of the malate-asparate hydrogen shuttle are the dominant neurochemical lesions.
The pathophysiological basis of acute-on-chronic liver failure.
TLDR
This review focuses upon how a precipitant such as an episode of gastrointestinal bleeding or sepsis may start a cascade of events that culminate in end-organ dysfunction and liver failure.
Plasma and CSF Benzodiazepine Receptor Ligand Concentrations in Cirrhotic Patients with Hepatic Encephalopathy: Relationship to Severity of Encephalopathy and to Pharmaceutical Benzodiazepine Intake
TLDR
It is suggested that pharmaceutic benzodiazepines administered to cirrhotic patients as sedatives or as part of endoscopic work-up could have contributed to the neurological impairment in some patients.
Aromatic and branched-chain amino acids in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy
Concentrations of the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine and the aromatic amino acids (AAAs) phenylalanine and tyrosine were measured in three areas of dissected brain
Amino Acid Changes in Autopsied Brain Tissue from Cirrhotic Patients with Hepatic Encephalopathy
TLDR
Brain tissue obtained at autopsy from nine cirrhotic patients dying in hepatic coma and from an equal number of controls was found to be within normal limits in all brain structures, suggesting the pathogenesis of hepatic encephalopathy resulting from chronic liver disease may be of significance.
Therapeutic efficacy of L‐ornithine‐L‐aspartate infusions in patients with cirrhosis and hepatic encephalopathy: Results of a placebo‐controlled, double‐blind study
TLDR
OA infusion appears to be a safe, effective treatment of chronic (persistent) manifest HE in cirrhotic patients and differential but uniformly significant efficacies in patients with manifest HE with respect to ammonia‐lowering, improvement in NCT times, and mental state gradation are presented.
Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats
TLDR
In this model of fulminant liver failure and associated brain edema, brain ammonia increases to levels associated with in vitro swelling of brain slices and glial cells, suggesting that osmogenic aminoacids such as glutamine and alanine may contribute to the selective astrocyte swelling seen in this condition.
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