Thiamine deficiency-related brain dysfunction in chronic liver failure.
End-stage chronic liver failure results in thiamine deficiency caused principally by depletion of liver thiamine stores. Chronic liver failure also leads to increased brain ammonia concentrations. Both ammonia and thiamine deficiency result in decreased activity of alpha-ketoglutarate dehydrogenase, a rate-limiting tricarboxylic acid cycle enzyme. Loss of enzyme activity results in a mitochondrial oxidative deficit in brain and consequent increases in brain lactate, oxidative/nitrosative stress, cellular energy impairment and release of proinflammatory cytokines, all of which have been described in brain in end-stage chronic liver failure. Synergistic effects of ammonia exposure and thiamine deficiency could explain the diencephalic and cerebellar symptomatology described in patients with "hepatic encephalopathy". Unsuspected brain lesions due to thiamine deficiency could explain the incomplete resolution of neuropsychiatric symptoms following the use of ammonia-lowering agents or liver transplantation in patients with end-stage chronic liver failure. These findings underscore the need for prompt, effective thiamine supplementation in all patients with chronic liver failure.
Butterworth
Roger F
RF
Neuroscience Research Unit, Saint-Luc Hospital (CHUM), University of Montreal, 1058, Saint-Denis Street, Montreal, QC H2X 3J4, Canada. roger.butterworth@umontreal.ca
D000328:Adult; D000368:Aged; D000641:Ammonia / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002908:Chronic Disease; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D017093:Liver Failure / Q000150:complications*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D013832:Thiamine Deficiency / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D014899:Wernicke Encephalopathy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
D000641:Ammonia; D007655:Ketoglutarate Dehydrogenase Complex