Vannata Barbara, Zucca Emanuele
Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):590-8. doi: 10.1182/asheducation-2014.1.590. Epub 2014 Nov 18.
Epidemiological studies have demonstrated an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. However, the strength of the association shows great geographic discrepancies, with higher relative risk in countries with high HCV prevalence. It remains unclear whether additional environmental and genetic factors are involved or if the international variability is simply a consequence of the variable infection prevalence. Therefore, a causal relationship remains controversial. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used, and the year of publication. The most convincing proof is the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after HCV eradication with IFN and ribavirin. However, the molecular mechanisms of the HCV-induced lymphomagenesis are mainly hypothetical. According to the model considered to be most plausible, lymphoma growth is a consequence of the continuous antigenic stimulation of the B-cell immunologic response induced by the chronic viral infection. This review summarizes the current epidemiological and biological evidence of a role of HCV in lymphomagenesis, describing the putative mechanisms for a causative relationship. The clinical characteristics and management difficulties of the HCV-associated lymphomas are also discussed. HCV treatment with IFN cannot be given safely in concomitance with cytotoxic lymphoma treatment because of hematological and liver toxicity. However, novel and better tolerated antiviral regimens are under development and will hopefully make the treatment of both lymphoma and hepatitis easier in the future.
流行病学研究表明，慢性丙型肝炎病毒（HCV）感染者发生B细胞淋巴瘤的风险增加。然而，这种关联的强度在地域上存在很大差异，在HCV高流行率国家相对风险更高。目前尚不清楚是否涉及其他环境和遗传因素，或者国际间的差异仅仅是感染率不同的结果。因此，因果关系仍存在争议。其他混杂因素可能会影响不同研究的可比性，包括HCV评估方法、正常对照的选择、所使用的淋巴瘤分类以及发表年份。最有说服力的证据是，主要限于某些惰性亚型的观察发现，使用干扰素和利巴韦林根除HCV后B细胞淋巴瘤出现消退。然而，HCV诱导淋巴瘤发生的分子机制主要是推测性的。根据被认为最合理的模型，淋巴瘤的生长是慢性病毒感染诱导的B细胞免疫反应持续抗原刺激的结果。本综述总结了目前关于HCV在淋巴瘤发生中作用的流行病学和生物学证据，描述了因果关系的假定机制。还讨论了HCV相关淋巴瘤的临床特征和治疗难点。由于血液学和肝脏毒性，不能在进行细胞毒性淋巴瘤治疗的同时安全地给予干扰素进行HCV治疗。然而，新型且耐受性更好的抗病毒方案正在研发中，有望在未来使淋巴瘤和肝炎的治疗都更加容易。
