title: New technologies - new insights into the pathogenesis of hepatic encephalopathy.
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.
authors.affiliation: Department of Clinical Science and Services, Royal Veterinary College, Hatfield, Hertfordshire, UK.
authors.forename: Luisa
authors.initials: L
authors.lastname: Baker
authors.affiliation: Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. Bernard.Lanz@nottingham.ac.uk.|Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. Bernard.Lanz@nottingham.ac.uk.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lanz
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK.
authors.forename: Fausto
authors.initials: F
authors.lastname: Andreola
authors.affiliation: Inter-Centre Unit of Digestive Diseases, Virgen Macarena - Virgen del Rocío University Hospitals, Sevilla, Spain.|Instituto de Biomedicina de Sevilla, Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ampuero
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Anisha
authors.initials: A
authors.lastname: Wijeyesekera
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Department of Health & Kinesiology, Texas A&M University, College Station, TX, USA.
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Deutz
mesh_terms: D000818:Animals; D006501:Hepatic Encephalopathy / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055432:Metabolomics / Q000379:methods* / Q000639:trends; D035683:MicroRNAs / Q000097:blood / Q000235:genetics
chemical_list: D035683:MicroRNAs
keywords: Genomics; Hepatic encephalopathy; Metabonomics; MicroRNA; Nuclear magnetic resonance spectroscopy; Targeted fluxomics