Balta Alexia Anastasia Stefania, Ignat Mariana Daniela, Barbu Raisa Eloise, Dumitru Caterina, Radaschin Diana Sabina, Bulza Valentin, Mateescu Costin Silvia Aura, Pleșea-Condratovici Catalin, Baroiu Liliana
Doctoral School of Biomedical Sciences, 'Dunarea de Jos' University, 800008 Galati, Romania.
Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University, 800008 Galati, Romania.
Healthcare (Basel). 2025 Aug 9;13(16):1953. doi: 10.3390/healthcare13161953.
: Chronic hepatitis C virus (HCV) infection is associated with a wide spectrum of extrahepatic manifestations, involving the immune, dermatologic, endocrine, vascular, and neuropsychiatric systems. Among these, mixed cryoglobulinemic vasculitis (CryoVas) remains one of the most clinically relevant complications. This work aims to provide a structured overview of HCV-related extrahepatic conditions and to analyze the clinical and virological outcomes of direct-acting antivirals (DAAs) in CryoVas patients. : We first categorized and reviewed extrahepatic manifestations of HCV across five major domains: immune, inflammatory/metabolic/vascular, dermatological, thyroid, and neuropsychiatric. Subsequently, we conducted a comparative analysis of five clinical studies evaluating the impact of DAA therapy in patients with CryoVas. Data on demographics, clinical symptoms, treatment regimens, sustained virological response, and clinical response were extracted and summarized. : HCV was found to be associated with numerous extrahepatic conditions, including mixed cryoglobulinemia, non-Hodgkin lymphoma, autoimmune thyroiditis, insulin resistance, and neurocognitive symptoms. In the CryoVas subgroup analysis, virological response rates were uniformly high (88.9-100%), but clinical remission varied significantly. Complete response ranged from 39% to 90%, highlighting a discrepancy between viral eradication and extrahepatic symptom resolution. These findings underscore the need for individualized follow-up and further investigation into persistent immunological dysfunction post-sustained virological response (SVR). However, clinical outcomes were more variable: complete response (CR) varied between 39% and 90%, partial response (PR) ranged from 4% to 42%, and no response (NR) was reported in 0% to 40% of cases. Although significant improvement in key manifestations such as purpura, arthralgia, and neuropathy was frequently observed, a subset of patients continued to exhibit residual or refractory symptoms despite achieving SVR. : HCV infection exerts multisystemic effects that extend beyond liver pathology. While DAAs offer near-universal virological clearance, the heterogeneous clinical response in CryoVas underscores the need for closer monitoring of extrahepatic outcomes. Future research should assess whether combining DAAs with immunomodulatory strategies can improve symptom control and long-term outcomes in patients with severe or refractory CryoVas.
慢性丙型肝炎病毒（HCV）感染与多种肝外表现相关，累及免疫、皮肤、内分泌、血管和神经精神系统。其中，混合性冷球蛋白血症性血管炎（CryoVas）仍然是临床上最相关的并发症之一。这项工作旨在对HCV相关的肝外疾病进行结构化概述，并分析直接作用抗病毒药物（DAA）在CryoVas患者中的临床和病毒学结局。：我们首先对HCV的肝外表现进行分类和回顾，涵盖五个主要领域：免疫、炎症/代谢/血管、皮肤、甲状腺和神经精神。随后，我们对五项评估DAA治疗对CryoVas患者影响的临床研究进行了比较分析。提取并总结了有关人口统计学、临床症状、治疗方案、持续病毒学应答和临床应答的数据。：发现HCV与多种肝外疾病相关，包括混合性冷球蛋白血症、非霍奇金淋巴瘤、自身免疫性甲状腺炎、胰岛素抵抗和神经认知症状。在CryoVas亚组分析中，病毒学应答率普遍较高（88.9%-100%），但临床缓解差异显著。完全缓解率在39%至90%之间，突出了病毒清除与肝外症状缓解之间的差异。这些发现强调了个体化随访的必要性，以及对持续病毒学应答（SVR）后持续免疫功能障碍进行进一步研究的必要性。然而，临床结局更具变异性：完全缓解（CR）在39%至90%之间变化，部分缓解（PR）在4%至42%之间，0%至40%的病例报告无应答（NR）。尽管经常观察到紫癜、关节痛和神经病变等关键表现有显著改善，但一部分患者尽管实现了SVR仍继续表现出残留或难治性症状。：HCV感染产生的多系统影响超出了肝脏病理范围。虽然DAA能实现几乎普遍的病毒清除，但CryoVas中临床应答的异质性强调了对肝外结局进行更密切监测的必要性。未来的研究应评估将DAA与免疫调节策略相结合是否能改善重度或难治性CryoVas患者的症状控制和长期结局。
