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New technologies - new insights into the pathogenesis of hepatic encephalopathy

Baker, L; Lanz, B; Andreola, F; Ampuero, J; Wijeyesekera, A; Holmes, E; Deutz, N; (2016) New technologies - new insights into the pathogenesis of hepatic encephalopathy. Metabolic Brain Disease , 31 (6) pp. 1259-1267. 10.1007/s11011-016-9906-y. Green open access

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Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which frequently accompanies acute or chronic liver disease. It is characterized by a variety of symptoms of different severity such as cognitive deficits and impaired motor functions. Currently, HE is seen as a consequence of a low grade cerebral oedema associated with the formation of cerebral oxidative stress and deranged cerebral oscillatory networks. However, the pathogenesis of HE is still incompletely understood as liver dysfunction triggers exceptionally complex metabolic derangements in the body which need to be investigated by appropriate technologies. This review summarizes technological approaches presented at the ISHEN conference 2014 in London which may help to gain new insights into the pathogenesis of HE. Dynamic in vivo13C nuclear magnetic resonance spectroscopy was performed to analyse effects of chronic liver failure in rats on brain energy metabolism. By using a genomics approach, microRNA expression changes were identified in plasma of animals with acute liver failure which may be involved in interorgan interactions and which may serve as organ-specific biomarkers for tissue damage during acute liver failure. Genomics were also applied to analyse glutaminase gene polymorphisms in patients with liver cirrhosis indicating that haplotype-dependent glutaminase activity is an important pathogenic factor in HE. Metabonomics represents a promising approach to better understand HE, by capturing the systems level metabolic changes associated with disease in individuals, and enabling monitoring of metabolic phenotypes in real time, over a time course and in response to treatment, to better inform clinical decision making. Targeted fluxomics allow the determination of metabolic reaction rates thereby discriminating metabolite level changes in HE in terms of production, consumption and clearance.

Type: Article
Title: New technologies - new insights into the pathogenesis of hepatic encephalopathy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s11011-016-9906-y
Publisher version: http://dx.doi.org/10.1007/s11011-016-9906-y
Language: English
Additional information: Copyright © Springer Science+Business Media New York 2016. The final publication is available at Springer via http://dx.doi.org/10.1007/s11011-016-9906-y
Keywords: Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, Neurosciences, Neurosciences & Neurology, Hepatic encephalopathy, Genomics, Nuclear magnetic resonance spectroscopy, MicroRNA, Metabonomics, Targeted fluxomics, Acute Liver-failure, Critical Flicker Frequency, Nitric-oxide Production, C-13 NMR-spectroscopy, In-vivo, Brain, Metabolism, Cirrhosis, Micrornas, Infusion
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 > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/1521939
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