Department of Hematology, Assistance Publique-Hôpitaux de Paris (APHP), Necker Hospital, Paris, France.
INSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Paris, France.
Ann Oncol. 2018 Jan 1;29(1):92-100. doi: 10.1093/annonc/mdx635.
In addition to liver disorders, hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to antiviral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated. Based on reported biological studies, several mechanisms of transformation seem however to emerge. A strong body of evidence supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to frank lymphoma, mostly of marginal zone subtype. By infecting lymphocytes, HCV could play a direct role in cellular transformation, particularly in de novo large B-cell lymphoma. Finally, HCV is associated with follicular lymphoma in a subset of patients. In this setting, it may be hypothesized that inflammatory cytokines stimulate proliferation and transformation of IgH-BCL2 clones that are increased during chronic HCV infection. Unraveling the pathogenesis of HCV-related B-cell lymphoproliferation is of prime importance to optimize therapeutic strategies, especially with the recent development of new direct-acting antiviral drugs.
除了肝脏疾病外，丙型肝炎病毒（HCV）也与肝外免疫表现和 B 细胞非霍奇金淋巴瘤（NHL）有关，尤其是边缘区淋巴瘤、新诊断或转化弥漫性大 B 细胞淋巴瘤，滤泡性淋巴瘤较少见。流行病学数据和临床观察表明 HCV 与淋巴增殖性疾病之间存在关联。HCV 在 NHL 中的致病作用也得到了抗病毒治疗反应的进一步支持。从 HCV 感染到明显淋巴瘤的发病机制仍需要进一步阐明。基于已报道的生物学研究，似乎出现了几种转化机制。大量证据支持间接转化机制的假设，即持续的抗原刺激导致从寡克隆扩展到单克隆扩展，有时甚至发展为明显的淋巴瘤，主要是边缘区亚型。HCV 通过感染淋巴细胞，可能在细胞转化中发挥直接作用，特别是在新诊断的大 B 细胞淋巴瘤中。最后，HCV 与一部分滤泡性淋巴瘤患者有关。在这种情况下，可以假设炎症细胞因子刺激 IgH-BCL2 克隆的增殖和转化，这些克隆在慢性 HCV 感染期间增加。解析 HCV 相关 B 细胞淋巴增殖的发病机制对于优化治疗策略至关重要，特别是随着新型直接作用抗病毒药物的最近发展。
