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丙型肝炎病毒在结肠组织中的肝外感染及其与丙型肝炎病毒发病机制的关系。

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis.

作者信息

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

机构信息

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.

出版信息

J Med Microbiol. 2016 Aug;65(8):703-712. doi: 10.1099/jmm.0.000272. Epub 2016 May 10.

Abstract

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.

摘要

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。

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