Maximum levels of hepatitis C virus lipoviral particles are associated with early and persistent infection
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2016-07-05Author
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<jats:title>Abstract</jats:title><jats:sec><jats:title>Background & Aims</jats:title><jats:p>Hepatitis C virus (<jats:styled-content style="fixed-case">HCV</jats:styled-content>) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle (<jats:styled-content style="fixed-case">LVP</jats:styled-content>). Experimental evidence indicates that <jats:styled-content style="fixed-case">LVP</jats:styled-content>s have decreased susceptibility to antibody‐mediated neutralisation and higher infectivity. This study tested the hypothesis that <jats:styled-content style="fixed-case">LVP</jats:styled-content>s are required to establish persistent infection, and conversely, low levels of <jats:styled-content style="fixed-case">LVP</jats:styled-content> in recent <jats:styled-content style="fixed-case">HCV</jats:styled-content> infection increase the probability of spontaneous <jats:styled-content style="fixed-case">HCV</jats:styled-content> clearance.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:styled-content style="fixed-case">LVP</jats:styled-content> in non‐fasting plasma was measured using the concentration of <jats:styled-content style="fixed-case">HCV RNA</jats:styled-content> bound to large >100 n<jats:sc>m</jats:sc> sized lipoproteins after <jats:italic>ex vivo</jats:italic> addition of a lipid emulsion, that represented the maximum concentration of <jats:styled-content style="fixed-case">LVP</jats:styled-content> (maxi‐<jats:styled-content style="fixed-case">LVP</jats:styled-content>). This method correlated with <jats:styled-content style="fixed-case">LVP</jats:styled-content> in fasting plasma measured using iodixanol density gradient ultracentrifugation. Maxi‐<jats:styled-content style="fixed-case">LVP</jats:styled-content> was measured in a cohort of 180 <jats:styled-content style="fixed-case">HCV</jats:styled-content> participants with recent <jats:styled-content style="fixed-case">HCV</jats:styled-content> infection and detectable <jats:styled-content style="fixed-case">HCV RNA</jats:styled-content> from the Australian Trial in Acute Hepatitis C (<jats:styled-content style="fixed-case">ATAHC</jats:styled-content>) and Hepatitis C Incidence and Transmission Study in prison (<jats:styled-content style="fixed-case">HITS</jats:styled-content>‐p) cohorts.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Spontaneous clearance occurred in 15% (27 of 180) of individuals. In adjusted analyses, low plasma maxi‐<jats:styled-content style="fixed-case">LVP</jats:styled-content> level was independently associated with spontaneous <jats:styled-content style="fixed-case">HCV</jats:styled-content> clearance (≤827 IU/ml; adjusted odds ratio 3.98, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content>: 1.02, 15.51, <jats:italic>P</jats:italic> = 0.047), after adjusting for interferon lambda‐3 rs8099917 genotype, estimated duration of <jats:styled-content style="fixed-case">HCV</jats:styled-content> infection and total <jats:styled-content style="fixed-case">HCV RNA</jats:styled-content> level.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Maxi‐<jats:styled-content style="fixed-case">LVP</jats:styled-content> is a biomarker for the maximum concentration of <jats:styled-content style="fixed-case">LVP</jats:styled-content> in non‐fasting samples. Low maxi‐<jats:styled-content style="fixed-case">LVP</jats:styled-content> level is an independent predictor of spontaneous clearance of acute <jats:styled-content style="fixed-case">HCV</jats:styled-content>.</jats:p></jats:sec>
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