Tonutti Antonio, Polverini Davide, De Nicola Stella, Ceribelli Angela, Soleri Matteo, De Santis Maria, Aghemo Alessio, Selmi Carlo, Pugliese Nicola
Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Milan, Italy.
Expert Rev Anti Infect Ther. 2025 Jan;23(1):19-30. doi: 10.1080/14787210.2024.2442475. Epub 2025 Jan 3.
Hepatitis C virus (HCV) infection represents a significant global health burden, particularly due to its extrahepatic immune-mediated manifestations, such as mixed cryoglobulinemia, associated vasculitis (CryoVas), and non-Hodgkin B-cell lymphoma (B-NHL), which pose significant challenges. The advent of direct-acting antiviral (DAA) has changed the therapeutic landscape for HCV-related complications.
This review explores the evolving epidemiology and management of HCV extrahepatic manifestation and lymphoproliferative disorders in the era of DAAs. It examines the efficacy of DAAs in controlling CryoVas and their complex role in HCV-related B-cell lymphoma. The literature search included studies on the immunological dynamics between HCV, CryoVas, and lymphoma, focusing on the impact of sustained virological response (SVR) on immune dysregulation, relapse risk, refractory disease, and patient stratification based on risk profiles.
DAAs have significantly improved the management of HCV-related CryoVas and autoimmune manifestations, but remain a challenge in refractory cases and the risk of lymphoma. Future strategies should focus on refining risk stratification and integrating new therapeutic approaches to better address immune dysregulation and associated complications.
丙型肝炎病毒（HCV）感染是一项重大的全球健康负担，尤其是因其肝外免疫介导的表现，如混合性冷球蛋白血症、相关血管炎（CryoVas）和非霍奇金B细胞淋巴瘤（B-NHL），这些都带来了重大挑战。直接抗病毒药物（DAA）的出现改变了HCV相关并发症的治疗格局。
本综述探讨了在DAA时代HCV肝外表现和淋巴增殖性疾病不断演变的流行病学及管理。它研究了DAA在控制CryoVas方面的疗效及其在HCV相关B细胞淋巴瘤中的复杂作用。文献检索包括关于HCV、CryoVas和淋巴瘤之间免疫动力学的研究，重点关注持续病毒学应答（SVR）对免疫失调、复发风险、难治性疾病以及基于风险特征的患者分层的影响。
DAA显著改善了HCV相关CryoVas和自身免疫表现的管理，但在难治性病例和淋巴瘤风险方面仍然是一项挑战。未来策略应侧重于完善风险分层并整合新的治疗方法，以更好地应对免疫失调及相关并发症。
