Abstract
Background
Chronic Hepatitis C Virus infection has been commonly linked to the development of autoimmunity, in part through activation of B cells. As well, B cells have been shown to play an important pathogenic role in Primary Biliary Cholangitis (PBC). Patients with concurrent HCV infection and PBC have an increased risk of more rapidly progressive disease, although the mechanism underlying this effect is poorly understood. However, it seemed plausible that HCV infection could enhance PBC-associated autoimmunity thereby worsening disease.
Aims
Therefore, the aim of our study was to determine the impact of HCV eradication upon serological markers of autoimmunity (ie. autoantibody production) and liver biochemistry in PBC patients infected with HCV.
Methods
We identified 3 HCV-infected patients who also had significant serum AMA titers, and were followed in the University of Calgary Liver Unit. All 3 patients were treated with non-interferon based direct-acting antiviral (DAA) therapies. One patient was on UDCA therapy (13 mg/kg/day) during the treatment period (elevated serum alkaline phosphatase levels). The remaining two patients were not on UDCA therapy due to intolerance in one, and normal serum alkaline phosphatase levels in the other. Virological response to DAA’s was assessed during and after therapy in all patients using a HCV Quantitative Nucleic Acid Test (Abbott), and serum liver biochemistries measured by Calgary Laboratory Services. Autoantibodies associated with autoimmune liver diseases, including PBC specifically, were measured before, during and after DAA treatment (Mitogen Advanced Diagnostics Laboratory, Calgary AB, Canada).
Results
All patients achieved a sustained virological response (SVR), as determined by a negative HCV RNA test 12 weeks post-DAA therapy. Titres of antimitochondrial 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 three patients exhibited a transient decrease in some autoantibody titres during DAA treatment, but these returned to baseline levels post-DAA therapy.
Conclusions
Our results suggest that ongoing HCV infection is not a significant driver of PBC-related autoimmunity/autoantibody production.
Funding Agencies
CIHRCal Wenzel Family Foundation Chair in Hepatology,