Abstract

There is an evidence of neurocognitive dysfunction even in the absence of advanced liver disease in chronic hepatitis C virus (HCV) infection. Brain metabolism has been investigated non-invasively using one-dimensional (1D) in vivo Magnetic Resonance Spectroscopy (MRS) over three decades. Even though highly concentrated cerebral metabolites (N-acetylaspartate, creatine, choline, glutamate/glutamine, myo-inositol) have been detected using MRS, other metabolites at low concentrations (~1–3 mM or less) including glutathione, aspartate and GABA are quite difficult to observe using 1D MRS. In order to resolve overlapping resonances from a number of metabolites, a remedy is to add a second spectral dimension to the existing 1D MRS. Localized two-dimensional correlated spectroscopy (L-COSY) has been developed over the last decade to enhance the spectral dispersion by using the second spectral dimension. We have evaluated this L-COSY technique in the frontal white/gray matter regions of 14 HCV+ (mean age of 56.2 years) and 14 HCV− (mean age of 46.6 years) subjects. Our preliminary results showed significantly increased myo-inositol and glutathione in the HCV+ compared to the HCV− subjects. Hence, glutathione and myo-inositol should be considered along with other metabolites as important markers of inflammation.

Highlights

  • The natural course of Hepatitis C virus (HCV) infection, which is transmitted via parenteral route, is modulated by both host and viral factors and typically tends to evolve towards chronicity, which will ensue in approximately 85% of cases following acute infection [1]

  • Our results showed significant increase of mI and GSH in the hepatitis C virus (HCV)+ patient group compared to healthy controls and demonstrated that the 2D Magnetic Resonance Spectroscopy (MRS) spectra allowed us to visualize and characterize the role of GSH in cerebral metabolism

  • Additional findings from this work include the quantitation of GSH, gamma-aminobutyric acid (GABA), Glu, Scy, and Asp using the 2D Localized twodimensional correlated spectroscopy (L-COSY) spectra postprocessed by the prior knowledge fitting (ProFit) algorithm

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Summary

Introduction

The natural course of Hepatitis C virus (HCV) infection, which is transmitted via parenteral route, is modulated by both host and viral factors and typically tends to evolve towards chronicity, which will ensue in approximately 85% of cases following acute infection [1]. Given that this virus affects approximately 3% of the world’s population [2], HCV infection represents a leading cause of chronic hepatitis, cirrhosis, end-stage liver failure, and hepatocellular carcinoma. Subtle cognitive complaints are reported that include difficulties in concentration and slowed processing speed These observations sparked a number of investigations that sought to characterize neuropathological changes in patients with HCV with mild (noncirrhotic) liver disease

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