Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis.
OBJECTIVE
Studies in acute liver failure show correlation between evidence of a systemic inflammatory response syndrome (SIRS) and progression of hepatic encephalopathy (HE). We tested the hypothesis that SIRS mediators, such as nitric oxide and proinflammatory cytokines, may exacerbate the neuropsychological effects of hyperammonemia in cirrhosis.


METHODS
Ten patients with cirrhosis were studied, 24-36 h after admission with clinical evidence of infection, and following its resolution. Hyperammonemia was induced by oral administration of an amino-acid (aa) solution mimicking hemoglobin composition. Inflammatory mediators, nitrate/nitrite, ammonia, aa profiles and a battery of neuropsychological tests were measured.


RESULTS
The hyperammonemia generated in response to the aa solution was similar prior to, and after resolution, of the inflammation (P=0.77). With treatment of the infection there were significant reductions in white blood cell count (WBC), C-reactive protein (CRP), nitrate/nitrite, interleukin-6, interleukin-1beta and tumour necrosis factor alpha. Induced hyperammonemia resulted in significant worsening of the neuropsychological scores when patients showed evidence of SIRS but not after its resolution.


CONCLUSIONS
The significant deterioration of neuropsychological test scores following induced hyperammonemia during the inflammatory state, but not after its resolution, suggests that the inflammation and its mediators may be important in modulating the cerebral effect of ammonia in liver disease.
Shawcross
Debbie L
DL
Liver Failure Group, Institute of Hepatology, University College London Medical School, 69-75, Chenies Mews, London WC1E 6HX, UK.
Davies
Nathan A
NA
Williams
Roger
R
Jalan
Rajiv
R
D000596:Amino Acids / Q000097:blood; D000641:Ammonia / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000276:immunology / Q000523:psychology; D006801:Humans; D022124:Hyperammonemia / Q000150:complications* / Q000276:immunology / Q000523:psychology; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000523:psychology; D018836:Inflammation Mediators / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications* / Q000276:immunology / Q000523:psychology; D008297:Male; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests; D011930:Reaction Time
D000596:Amino Acids; D018836:Inflammation Mediators; D000641:Ammonia; D002097:C-Reactive Protein