Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection

Simon Bridge, David Sheridan, Daniel Felmlee, Søren Nielsen, Howard Thomas, Simon Taylor-Robinson, Robert Dermot Neely, Geoffrey Toms, Margaret Bassendine

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Background: The density of hepatitis C virus (HCV) in plasma is heterogeneous but the factors which influence this are poorly understood. Evidence from animal models and cell culture suggest that low-density apolipoprotein B (apoB)-associated HCV lipoviral particles (LVP) are more infectious than high-density HCV. 
Objective: To measure LVP in patients with chronic hepatitis C genotype 1 (CHC-G1) and examine metabolic determinants of LVP load. 
Patients: 51 patients with CHC-G1 infection. 
Methods: Fasting lipid profiles and homeostasis model assessment of insulin resistance (HOMA-IR) were determined in 51 patients with CHC-G1. LVP and non-LVP viral load were measured by real-time PCR of plasma at density <1.07 g/ml and > 1.07 g/ml, respectively, following iodixanol density gradient ultracentrifugation. The LVP ratio was calculated using the formula: LVP/(LVP + non-LVP). 
Results: The mean LVP ratio was 0.241 but varied 25-fold (from 0.029 to 0.74). Univariate analysis showed that the LVP ratio correlated with HOMA-IR (p = 0.004) and the triglyceride/high-density lipoprotein cholesterol (TG/HDLC) ratio (p = 0.004), but not with apoB. In multivariate analysis, HOMA-IR was the main determinant of LVP load (log(10)IU/ml) (R(2) = 16.6%; p = 0.037) but the TG/HDL-C ratio was the strongest predictor of the LVP ratio (R(2) = 24.4%; p = 0.019). Higher LVP ratios were associated with non-response to antiviral therapy (p = 0.037) and with greater liver stiffness (p = 0.001). 
Conclusion: IR and associated dyslipidaemia are the major determinants of low-density apoB-associated LVP in fasting plasma. This provides a possible mechanism to explain why IR is associated with more rapidly progressive liver disease and poorer treatment outcomes.
Original languageEnglish
Pages (from-to)680-687
JournalGut
Volume60
Issue number5
DOIs
Publication statusPublished - 2011

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