Nguyen Henry H, Khathlan Abdullah, Fritzler Marvin J, Swain Mark G
Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Canada.
University of Calgary, Calgary, AB, Canada.
BMC Gastroenterol. 2018 Jun 25;18(1):97. doi: 10.1186/s12876-018-0826-7.
Chronic 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.
A 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.
Within 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.
慢性丙型肝炎病毒（HCV）感染通常与自身免疫的发展有关，部分原因是通过B细胞的激活。B细胞也被认为在自身免疫性肝病原发性胆汁性胆管炎（PBC）中起致病作用。同时患有PBC和HCV感染的患者发生更进展性疾病的风险增加，尽管这种效应的潜在机制尚不清楚。本研究旨在利用一组同时患有PBC和HCV的患者病例系列，评估HCV根除对自身免疫/自身抗体产生的潜在影响。
一个病例系列评估了三名同时患有PBC-HCV感染的患者，他们接受了基于非干扰素的直接作用抗病毒药物（DAA）治疗HCV。三名患者中的一名在治疗期间接受了熊去氧胆酸（UDCA；13mg/kg/天）。使用HCV定量核酸检测（雅培）评估对DAA的持续病毒学应答（SVR）。在DAA治疗前、治疗期间和治疗后，检测与自身免疫性肝病（包括PBC）相关的自身抗体和肝脏生化指标（加拿大卡尔加里丝裂原高级诊断实验室）。所有患者在DAA治疗12周后HCV RNA检测呈阴性，从而确定达到了SVR。尽管成功根除了HCV，但抗线粒体抗体（AMA-M2）、抗支链2-氧代酸脱氢酶复合物和2-氧代戊二酸脱氢酶复合物（抗3E-BPO）以及抗含三联基序蛋白21（TRIM21/Ro52）的滴度保持不变。三名患者中的两名在DAA治疗期间某些自身抗体滴度出现短暂下降，但在DAA治疗后恢复到基线水平。
在病例系列的局限性内，我们的结果表明，HCV合并感染可能不是PBC相关自身免疫/自身抗体产生的重要驱动因素。然而，需要更大的样本量来真正评估HCV根除对自身抗体产生的影响。
