Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin

Aliment Pharmacol Ther. 2009 Jun 15;29(12):1282-90. doi: 10.1111/j.1365-2036.2009.04012.x. Epub 2009 Apr 8.

Abstract

Background: Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides.

Aim: To determine whether baseline lipid levels predicted treatment outcome.

Methods: Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome.

Results: There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001).

Conclusions: Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Apolipoproteins B / genetics*
  • Apolipoproteins B / metabolism
  • Cholesterol / genetics*
  • Cholesterol / metabolism
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Retrospective Studies
  • Ribavirin / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Apolipoproteins B
  • Interferon-alpha
  • Ribavirin
  • Cholesterol