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Maximum levels of hepatitis C virus lipoviral particles are associated with early and persistent infection

Lookup NU author(s): Dr David Sheridan, Fiona Fenwick, Emeritus Professor Margaret Bassendine


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Background & Aims: Hepatitis C virus (HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle (LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody-mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance. Methods: LVP in non-fasting plasma was measured using the concentration of HCV RNA bound to large > 100 nM sized lipoproteins after ex vivo addition of a lipid emulsion, that represented the maximum concentration of LVP (maxi-LVP). This method correlated with LVP in fasting plasma measured using iodixanol density gradient ultracentrifugation. Maxi-LVP was measured in a cohort of 180 HCV participants with recent HCV infection and detectable HCV RNA from the Australian Trial in Acute Hepatitis C (ATAHC) and Hepatitis C Incidence and Transmission Study in prison (HITS-p) cohorts. Results: Spontaneous clearance occurred in 15% (27 of 180) of individuals. In adjusted analyses, low plasma maxi-LVP level was independently associated with spontaneous HCV clearance (<= 827 IU/ml; adjusted odds ratio 3.98, 95% CI: 1.02, 15.51, P = 0.047), after adjusting for interferon lambda-3 rs8099917 genotype, estimated duration of HCV infection and total HCV RNA level. Conclusions: Maxi-LVP is a biomarker for the maximum concentration of LVP in non-fasting samples. Low maxi-LVP level is an independent predictor of spontaneous clearance of acute HCV.

Publication metadata

Author(s): Sheridan DA, Hajarizadeh B, Fenwick FI, Matthews GV, Applegate T, Douglas M, Neely D, Askew B, Dore GJ, Lloyd AR, George J, Bassendine MF, Grebely J

Publication type: Article

Publication status: Published

Journal: Liver International

Year: 2016

Volume: 36

Issue: 12

Pages: 1774-1782

Print publication date: 01/12/2016

Online publication date: 05/07/2016

Acceptance date: 21/05/2016

ISSN (print): 1478-3223

ISSN (electronic): 1478-3231

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/liv.13176


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Funder referenceFunder name
National Health and Medical Research Council of Australia
National Health and Medical Research Council Practitioner Research Fellowships
Robert W. Storr Bequest to the Sydney Medical Foundation
University of Sydney
Australian Government Department of Health and Ageing
National Health and Medical Research Council Career Development Fellowship
Research Grant from The Newcastle upon Tyne Healthcare Charity, Newcastle upon Tyne, United Kingdom
1006759National Health and Medical Research Council of Australia (NHMRC)
1047417National Health and Medical Research Council of Australia (NHMRC)
1053206National Health and Medical Research Council of Australia (NHMRC)