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.

Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

“…were identified. A previous study showed deregulation of these metabolic cycles and deregulation of amino acid metabolism in the plasma and urine of hepatitis E patients (46). In contrast to those results, a decrease in the level of lactate dehydrogenase was observed here, suggesting an absence of lactic acidosis in swine during hepatitis E virus infection.…”

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

“…Among the various tools used for metabolomics, nuclear magnetic resonance (NMR) spectroscopy has emerged as an useful and powerful method due to its noninvasiveness, rapidity, reproducibility, need for small sample volumes, and high accuracy in metabolic profiling2324. NMR based metabolomics approach has been used to understand the metabolic dysregulation in humans upon viral infections like hepatitis252627 and HIV2829.…”

1 H Nuclear Magnetic Resonance Metabolomics of Plasma Unveils Liver Dysfunction in Dengue Patients

“…More recently, metabolomics, the study of low-molecular-weight metabolites of physiological relevance, has proved an important tool for studying the changes in host metabolism during the course of viral infections (13)(14)(15)(16)(17). Since the metabolic resources crucial for viral replication are provided by host cells, the detection of changes in the metabolic profile associated with the pathological condition could help with the identification of markers of prognostic and diagnostic importance as well as the development of specific treatment strategies.…”