Metabolic characterization of the natural progression of chronic hepatitis B

Abstract

BackgroundWorldwide, over 350 million people are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing progressive liver diseases. The confinement of HBV replication to the liver, which also acts as the central hub for metabolic and nutritional regulation, emphasizes the interlinked nature of host metabolism and the disease. Still, the metabolic processes operational during the distinct clinical phases of a chronic HBV infection—immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis phases—remains unexplored.MethodsTo investigate this, we conducted a targeted metabolomics approach on serum to determine the metabolic progression over the clinical phases of chronic HBV infection, using patient samples grouped based on their HBV DNA, alanine aminotransferase, and HBeAg serum levels.ResultsOur data illustrate the strength of metabolomics to provide insight into the metabolic dysregulation experienced during chronic HBV. The immune tolerant phase is characterized by the speculated viral hijacking of the glycerol-3-phosphate–NADH shuttle, explaining the reduced glycerophospholipid and increased plasmalogen species, indicating a strong link to HBV replication. The persisting impairment of the choline glycerophospholipids, even during the inactive carrier phase with minimal HBV activity, alludes to possible metabolic imprinting effects. The progression of chronic HBV is associated with increased concentrations of very long chain triglycerides together with citrulline and ornithine, reflective of a dysregulated urea cycle peaking in the HBV envelope antigen-negative phase.ConclusionsThe work presented here will aid in future studies to (i) validate and understand the implication of these metabolic changes using a thorough systems biology approach, (ii) monitor and predict disease severity, as well as (iii) determine the therapeutic value of the glycerol-3-phosphate–NADH shuttle.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0318-8) contains supplementary material, which is available to authorized users.

Chronic hepatitis B virus infection and risk of dyslipidaemia: A cohort study

“…Likewise, a study using an NMR‐based metabolomics approach showed that HBx disrupts the metabolism of glucose, lipids and nucleic acids . The results from targeted metabolomics analyses have also shown that HBV is capable of altering the glycerophospholipids and triglyceride synthesis pathways resulting in reduced serum levels of lipids . Such defective lipid metabolism in liver cells, along with ongoing HBV replication, may subsequently reduce the risk for developing dyslipidaemia.…”

“…21 The results from targeted metabolomics analyses have also shown that HBV is capable of altering the glycerophospholipids and triglyceride synthesis pathways resulting in reduced serum levels of lipids. 22 Such defective lipid metabolism in liver cells, along with ongoing HBV replication, may subsequently reduce the risk for developing dyslipidaemia. On the other hand, adiponectin levels, which ameliorate insulin resistance as an anti-diabetic and anti-atherogenic adipokine, were positively associated with HBV viral load in overweight to obese HBV-infected subjects.…”

Predicting human health from biofluid-based metabolomics using machine learning

“…Cancer represented the largest category, with 14 studies 11,12,25,29,[31][32][33][34][35][36][37][38][39] ; cardiovascular 28 , rheumatologic 26 , ‡ , renal ‡ , and respiratory 16 diseases were represented by only one or two studies. Other health states with a small to medium number of studies included neuro/neuropsychiatric 18,19 , endocrine 21,24,40,41 , and infectious disease 14,15,27,30,42,43 , as well as a general 'other' category 17,[44][45][46] .…”

“…Metabolomics rapidly supplies information on thousands of molecules, and represents a method for biofluid-based diagnostics [7][8][9] . To date, serum, plasma, urine and cerebrospinal fluid (CSF) metabolomics has been applied to many health states, ranging from cancers [10][11][12][13] and infectious diseases 14,15 to Chronic Obstructive Pulmonary Disease (COPD) 16 , smoking 17 and Alzheimer's disease 18,19 . These studies are regularly performed using analytical instrumentation like liquid or gas chromatography mass spectrometry (LC-MS and GC-MS respectively) as well as nuclear magnetic resonance (NMR) 20 .…”

Electromembrane Extraction of Highly Polar Compounds: Analysis of Cardiovascular Biomarkers in Plasma

“…The optimized method was then combined with fast-liquid chromatography-tandem mass spectrometry (Fast-LC-MS/MS) for further evaluation of response function and dynamic range. ME was evaluated by comparing the developed extraction method to a sample pre-treatment method conventionally used in metabolomics, i.e., protein precipitation using methanol (PP-MeOH) [26,27]. Finally, the developed EME-LC-MS/MS method was applied to the analysis of 40 plasma samples and compared to PP-MeOH to show the strength of the method.…”