Autoantibody to apolipoprotein A-1 in hepatitis C virus infection: a role in atherosclerosis?

Simon H. Bridge, Sabrina Pagano, Meleri Jones, Graham R. Foster, Dermot Neely, Nicolas Vuilleumier, Margaret F. Bassendine

One to three per cent of the world's population has hepatitis C virus (HCV) infection, which is not only a major cause of liver disease and cancer but also associated with an increased risk of atherosclerosis, despite an ostensibly favourable lipid profile. Autoantibodies are frequent in HCV infection and emerging evidence shows that autoantibodies could be valuable for cardiovascular disease (CVD) risk stratification. This study investigated a novel independent biomarker of CVD, autoantibodies to apolipoprotein A-1 (anti-apoA-1 IgG) and lipids in patients with chronic HCV before, during and after direct-acting anti-viral (DAA) therapy. Eighty-nine blinded serum samples from 27 patients with advanced chronic HCV were assayed for lipids and anti-apoA-1 IgG by ELISA. Pre-treatment HCV viral load correlated with high-density lipoprotein cholesterol (HDL-C, r = 0.417; p = 0.042) and negatively with apolipoprotein (apo)B (r = - 0.497; p = 0.013) and markers of CVD risk, the apoB/apoA-1 ratio (r = - 0.490; p = 0.015) and triglyceride level (TG)/HDL-C ratio (r = - 0.450; p = 0.031). Fourteen (52%) of 27 patients had detectable anti-apoA-1 IgG autoantibodies pre-treatment; only two became undetectable with virological cure. Autoantibody-positive sera had lower apoA-1 (p = 0.012), HDL-C (p = 0.009) and total cholesterol (p = 0.006) levels. This is the first report of the presence of an emerging biomarker for atherosclerosis, anti-apoA-1 IgG, in some patients with HCV infection. It may be induced by apoA-1 on the surface of HCV lipoviral particles. The autoantibodies inversely correlate with apoA-1 and HDL levels and may render HDL dysfunctional. Whether these hypothesis-generating findings have clinical implications in HCV patients requires further study.