Autoantibody positivity in chronic hepatitis C pre- and post-direct-acting antiviral therapy: a prospective multicenter south Korean study

Abstract

Background: Hepatitis C virus (HCV) infection causes extrahepatic manifestations involving B-cell dysregulation and autoantibody production. This study aimed to elucidate the positivity rates of four autoantibodies [anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver kidney microsomal type 1 (anti-LKM1), and anti-mitochondrial antibody (AMA)] in patients with chronic hepatitis C (CHC) before and after direct-acting antiviral (DAA) therapy compared to those in healthy controls.

Methods: This study enrolled prospectively collected plasma samples from 201 CHC patients [median age, 62 years; 49.8% women; 100% sustained virological response (SVR)] from eight hospitals before and after DAA therapy and 127 healthy individuals. Autoantibodies were detected using indirect immunofluorescence.

Results: The positivity rate of ANA was higher in CHC patients than in healthy controls (32.3% vs. 21.3%, P=0.03) at pretreatment (PreTx) and decreased at SVR (32.3% vs. 23.9%, P=0.009). Female sex and higher globulin levels were related to ANA positivity in the control and CHC patient groups. Thirty-seven (57%) of 65 patients with ANA-positive HCV at PreTx maintained ANA-positivity at SVR. Among the 136 ANA-negative patients at PreTx, 11 (8%) showed newly positive ANA conversion at SVR. Patients with ANA positivity at SVR (n=48) were older and had a higher proportion of advanced liver disease than ANA-negative patients (n=153).

Conclusions: ANA positivity was observed in one-third of CHC patients at PreTx, which was significantly higher than that in healthy controls and decreased after SVR. CHC patients with ANA positivity after SVR were older and had more advanced liver disease than those with ANA negativity, suggesting persistent immune dysregulation after cure.