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Metabonomic analysis of hepatitis E patients shows deregulated metabolic cycles and abnormalities in amino acid metabolism.

Abstract
Hepatitis E, which is endemic to resource-poor regions of the world, is largely an acute and self-limiting disease, but some patients have an increased susceptibility to develop fulminant hepatitis. The pathogenesis of hepatitis E in humans is poorly characterized. To understand the metabolic pathways involved in the pathophysiology of hepatitis E, we have used (1) H nuclear magnetic resonance spectroscopy to quantify various metabolites in the plasma and urine of the patients with hepatitis E. These were compared with specimens from patients with acute hepatitis B as disease controls and healthy volunteers. Data were analysed using chemometric statistical methods and metabolite databases. The main metabonomic changes found in patients with hepatitis E, but not in those with hepatitis B, included increased plasma levels of L-isoleucine, acetone, and glycerol, reduced plasma levels of glycine, and reduced urinary levels of imidazole, 3-aminoisobutanoic acid, 1-methylnicotinamide, biopterin, adenosine, 1-methylhistidine, and salicyluric acid. Patients with hepatitis E or B both showed increased levels of plasma and urinary L-proline and decreased levels of various other metabolites. Pathway analysis tools suggest the involvement of glycolysis, tricarboxylic acid cycle, urea cycle, and amino acid metabolism in patients with acute hepatitis E. These findings may help better understand the clinical and biochemical manifestations in this disease and the underlying pathophysiologic processes. Based on our findings, it would be worthwhile determining whether patients with hepatitis E are more prone to develop lactic acidosis and ketosis compared with other forms of viral hepatitis.
AuthorsS U Munshi, S Taneja, N S Bhavesh, J Shastri, R Aggarwal, S Jameel
JournalJournal of viral hepatitis (J Viral Hepat) Vol. 18 Issue 10 Pg. e591-602 (Oct 2011) ISSN: 1365-2893 [Electronic] England
PMID21914081 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2011 Blackwell Publishing Ltd.
Chemical References
  • Amino Acids
Topics
  • Adult
  • Amino Acids (metabolism)
  • Female
  • Hepatitis B (physiopathology)
  • Hepatitis E (physiopathology)
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolic Networks and Pathways (genetics)
  • Metabolomics
  • Middle Aged
  • Plasma (chemistry)
  • Urine (chemistry)

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