A case series evaluating the impact of Hepatitis C eradication using direct acting antivirals on primary biliary cholangitis-associated autoimmunity

Abstract

BackgroundChronic Hepatitis C Virus (HCV) infection has been commonly linked to the development of autoimmunity, in part through activation of B cells. B cells are also postulated to play a pathogenic role in the autoimmune liver disease Primary Biliary Cholangitis (PBC). Patients with concurrent PBC and HCV infection carry an increased risk of more progressive disease, although the mechanism underlying this effect is poorly understood. Utilizing a case series of patients with concurrent PBC and HCV, the aim of this study was to evaluate for the potential impact of HCV eradication upon autoimmunity/autoantibody production.Case presentationA case series evaluating three patients with co-existing PBC-HCV infection receiving non-interferon based HCV treatments with direct-acting antivirals (DAA). One of three patient received Ursodeoxycholic acid (UDCA; 13 mg/kg/day) during the treatment period. Sustained virological response (SVR) to DAA’s was assessed using a HCV Quantitative Nucleic Acid Test (Abbott). Autoantibodies associated with autoimmune liver diseases (including PBC) and liver biochemistry, were measured before, during and after DAA treatment (Mitogen Advanced Diagnostics Laboratory, Calgary, Canada).All patients achieved an SVR, as determined by negative HCV RNA test 12 weeks post-DAA therapy. Titres of anti-mitochondrial antibodies (AMA-M2), anti- branched-chain 2-oxo-acid dehydrogenase complex and 2-oxo glutarate dehydrogenase complex (anti-3E-BPO), and anti- tripartite motif-containing protein 21 (TRIM21/Ro52) remained unchanged, despite successful HCV eradication. Two of the three patients exhibited a transient decrease in some autoantibody titres during DAA treatment, but these returned to baseline levels post-DAA therapy.ConclusionsWithin the limitations of a case series, our results suggest that HCV co-infection may not be a significant driver of PBC-related autoimmunity/autoantibody production. However, a larger n-value is required to truly assess for the effect of HCV eradication on autoantibody production.

Prevalence and Outcome of Serum Autoantibodies in Chronic Hepatitis C Patients Undergoing Direct-Acting Antiviral Treatment

“…There are only a few reports in the literature addressing the role of DAAs in clearing autoimmune serology in chronic hepatitis C patients and our results are in full accordance with these previous investigations ( 27 , 28 , 31 ). As only small case series have been published on this topic thus far ( 27 , 28 , 31 ), our report further contributes to and strengthens the notion of HCV being responsible for undermining immune tolerance in chronically infected patients. Besides, more than half of the patients (no.…”

Direct‐Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis

“…Interferon (IFN)‐free or direct‐acting antiviral (DAA) therapies have provided major advances in the treatment of HCV, with greater than 90% of patients achieving sustained viral response (SVR) with most regimens, and have been shown to be safe and effective in patients with associated autoimmune conditions . The impact of DAA treatment on patients with HCV with elevated serum markers of AIH and transaminases, with or without the presence of histopathologic features of AIH, is not clear in the literature except for brief discussions in a few case reports .…”