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Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

Shawcross, DL; Davies, NA; Williams, R; Jalan, R; (2004) Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. JOURNAL OF HEPATOLOGY , 40 (2) 247 - 254. 10.1016/j.jhep.2003.10.016. Green open access

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Abstract

Background/Aims: 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, interieukin-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. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Type: Article
Title: Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis
Location: BIRMINGHAM, ENGLAND
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jhep.2003.10.016
Keywords: minimal hepatic encephalopathy, neuropsychological function, proinflammatory cytokines, amino-acid solution, NECROSIS-FACTOR-ALPHA, HEPATIC-ENCEPHALOPATHY, SEPTIC ENCEPHALOPATHY, GLUTAMINE CHALLENGE, BLOOD AMMONIA, BRAIN, LIVER, MECHANISMS, SEPSIS, HEMOGLOBIN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Education
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/301
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