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

Bridge, Simon, Sheridan, David, Felmlee, Daniel, Nielsen, Søren, Thomas, Howard, Taylor-Robinson, Simon, Neely, Robert Dermot, Toms, Geoffrey and Bassendine, Margaret (2011) Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection. Gut, 60 (5). pp. 680-687. ISSN 0017-5749

Full text not available from this repository. (Request a copy)

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.

Item Type:	Article
Uncontrolled Keywords:	sustained virological response, liver fibrosis, plus ribavirin, metabolic system, in-vivo, receptor, therapy
Subjects:	C700 Molecular Biology, Biophysics and Biochemistry
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Linda Barlow
Date Deposited:	29 Jan 2013 16:56
Last Modified:	10 Oct 2019 23:01
URI:	http://nrl.northumbria.ac.uk/id/eprint/11059

Downloads