Increased serum oxysterol concentrations in patients with chronic hepatitis C virus infection

Biochem Biophys Res Commun. 2014 Apr 11;446(3):736-40. doi: 10.1016/j.bbrc.2014.01.176. Epub 2014 Feb 10.

Abstract

Oxidative stress and dysregulated cholesterol metabolism are characteristic features of chronic hepatitis C virus infection (CHC). Therefore, we analyzed serum oxysterol profiles in CHC patients and examined the significance of oxysterols in CHC. The concentrations of 7α-hydroxycholesterol, 4β-hydroxycholesterol and 25-hydroxycholesterol as determined by LC-ESI-MS/MS were significantly elevated by +236%, +29% and +44%, respectively, in CHC patients compared with controls. Moreover, the elevated levels were significantly decreased by anti-viral therapy using PEGylated-interferon and ribavirin for 3 months. In contrast, 24S-hydroxycholesterol, 27-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one concentrations were not affected by CHC or anti-viral treatment. These results suggest that some oxysterols that are elevated in CHC are produced by cholesterol autoxidation due to oxidative stress or inflammation in the liver. Oxysterols may represent novel targets for the inhibition of disease progression and the prevention of hepatocarcinogenesis in CHC patients.

Keywords: Anti-viral therapy; Chronic hepatitis C virus infection; Oxysterol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • Case-Control Studies
  • Female
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Hydroxycholesterols / blood*
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • Oxidative Stress
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Tandem Mass Spectrometry / methods

Substances

  • Antiviral Agents
  • Hydroxycholesterols
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • cholest-5-ene-3,4-diol
  • Polyethylene Glycols
  • Ribavirin
  • cholest-5-en-3 beta,7 alpha-diol
  • 25-hydroxycholesterol
  • peginterferon alfa-2b