Hetta Helal F, Mekky Mohamed A, Khalil Nasr K, Mohamed Wegdan A, El-Feky Mohamed A, Ahmed Shabaan H, Daef Enas A, Medhat Ahmed, Nassar Mahmoud I, Sherman Kenneth E, Shata Mohamed Tarek M
Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA.
Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
J Med Microbiol. 2016 Aug;65(8):703-712. doi: 10.1099/jmm.0.000272. Epub 2016 May 10.
Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extra-hepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-α and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (Treg) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic Treg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.
肝外区域可能与丙型肝炎病毒(HCV)持续感染及肝外表现有关。因此,我们研究了慢性丙型肝炎(CHC)患者结肠组织中的HCV感染情况及其与HCV发病机制的关系。从三组CHC感染患者中获取结肠活检组织:未经治疗组(TN;n = 12)、抗HCV治疗(聚乙二醇化干扰素-α和利巴韦林)无应答组(NR;n = 10)和持续病毒学应答组(SVR;n = 10),并从第四组健康对照组(n = 10)获取活检组织。检查肝活检组织以评估炎症和纤维化情况。通过免疫组织化学检测HCV感染及结肠调节性T细胞(Treg)频率。在TN组42%的B细胞和巨噬细胞/单核细胞中检测到HCV核心蛋白和NS3蛋白,NR组分别为50%和30%,但在SVR组或对照组中未检测到。表达HCV蛋白的细胞数量与HCV病毒载量及结肠Treg频率均呈正相关。发现表达HCV的细胞与肝脏炎症和纤维化均呈显著负相关。我们的研究提供了证据表明HCV可感染结肠的B细胞和巨噬细胞。结肠组织中HCV感染与HCV病毒载量及肝脏病理之间的相关性强调了这种肝外感染在HCV发病机制及治疗反应中的重要性。