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.