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 vivo 13C 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.
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Abbreviations
- ALF:
-
Acute liver failure
- ALI:
-
Acute liver injury
- APAP:
-
Acetaminophen
- BDL:
-
Bile duct-ligation
- CFF:
-
Critical flicker frequency
- CPP:
-
Cerebral perfusion pressure
- DAMP:
-
Damage-associated molecular pattern molecules
- GLS:
-
Glutaminase
- HCC:
-
Hepatocellular carcinoma
- HE:
-
Hepatic encephalopathy
- MHE:
-
Minimal hepatic encephalopathy
- miRNA:
-
Micro RNA
- MRS:
-
Magnetic resonance spectroscopy
- NMR:
-
Nuclear magnetic resonance
- PHES:
-
Psychometric hepatic encephalopathy score
- TCA:
-
Tricarboxylic acid cycle
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Acknowledgments
The authors warmly thank Dr. Boris Görg for his role as writing coordinator for this review article. Bernard Lanz gratefully acknowledges Dr. Cristina Cudalbu, Dr. Valérie McLin, Dr. Olivier Braissant and Dr. Rolf Gruetter for their contributions in the 13C MRS project. The 13C MRS study was supported by Centre d’Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL, the Leenaards and Jeantet Foundations and SNF grant 131087.
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Luisa Baker and Bernard Lanz contributed equally to the present work and thus share first authorship.
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Baker, L., Lanz, B., Andreola, F. et al. New technologies – new insights into the pathogenesis of hepatic encephalopathy. Metab Brain Dis 31, 1259–1267 (2016). https://doi.org/10.1007/s11011-016-9906-y
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DOI: https://doi.org/10.1007/s11011-016-9906-y