Ferri Clodoveo, Sebastiani Marco, Giuggioli Dilia, Colaci Michele, Fallahi Poupak, Piluso Alessia, Antonelli Alessandro, Zignego Anna Linda
Clodoveo Ferri, Marco Sebastiani, Dilia Giuggioli, Michele Colaci, Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy.
World J Hepatol. 2015 Mar 27;7(3):327-43. doi: 10.4254/wjh.v7.i3.327.
The clinical course of chronic hepatitis C virus (HCV) infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinico-epidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells non-Hodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients' populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.
慢性丙型肝炎病毒（HCV）感染的临床病程特点是可能出现肝脏和肝外疾病。HCV对淋巴组织的嗜性导致了几种免疫介导的疾病；在高比例的HCV感染患者中常见的多克隆 - 寡克隆B淋巴细胞扩增，导致了不同自身抗体和免疫复合物的产生，如混合冷球蛋白。这些血清学改变可能是多种自身免疫性或肿瘤性疾病的特征。由循环混合冷球蛋白在小血管沉积引起的冷球蛋白血症性血管炎是HCV驱动的免疫介导和淋巴增殖性疾病的典型代表；有趣的是，在某些情况下，该疾病可能演变为明显的恶性淋巴瘤。此外，一些临床流行病学和实验室研究表明HCV具有致癌潜力；除了肝细胞癌是最常见的与HCV相关的恶性肿瘤外，HCV在相当比例的孤立B细胞非霍奇金淋巴瘤患者中也被充分证明具有致病作用。同一病毒也可能参与乳头状甲状腺癌的发病机制，乳头状甲状腺癌是一种罕见的肿瘤性疾病，可能使与HCV相关的甲状腺受累情况复杂化。HCV感染患者通常无症状，或可能仅出现肝脏改变，而少数但具有临床相关性的患者可能会发生一种或多种自身免疫性和/或肿瘤性疾病。鉴于不同国家患者群体中其患病率差异很大，可以推测其他共同因素，即遗传和/或环境因素，在HCV相关肝外疾病发病机制中的潜在作用。
