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/HDL-C) ratio (p=0.004), but not with apoB. In multivariate analysis, HOMA-IR was the main determinant of LVP load (log10IU/ml) (R2=16.6%; p=0.037) but the TG/HDL-C ratio was the strongest predictor of the LVP ratio (R2=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.
- metabolic syndrome X
- hepatitis C
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Funding Supported by the Medical Research Council (G0502028) and the Newcastle upon Tyne Healthcare Charity. The funders had no role in the study design, data collection and analysis. HCT and SDT-R were supported by the NIHR Biomedical Facility at Imperial College London.
Competing interests None.
Ethics approval This study was conducted with the approval of the Northumberland Research ethics committee (REC number-07/H0902/45).
Provenance and peer review Not commissioned; externally peer reviewed.