title: 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.
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: S U
authors.initials: SU
authors.lastname: Munshi
authors.forename: S
authors.initials: S
authors.lastname: Taneja
authors.forename: N S
authors.initials: NS
authors.lastname: Bhavesh
authors.forename: J
authors.initials: J
authors.lastname: Shastri
authors.forename: R
authors.initials: R
authors.lastname: Aggarwal
authors.forename: S
authors.initials: S
authors.lastname: Jameel
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000503:physiopathology; D016751:Hepatitis E / Q000503:physiopathology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D055432:Metabolomics; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D014556:Urine / Q000737:chemistry
chemical_list: D000596:Amino Acids