Lauletta Gianfranco, Russi Sabino, Pavone Fabio, Vacca Angelo, Dammacco Franco
Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Piazza G. Cesare, 11-70124, Bari, Italy.
Arthritis Res Ther. 2017 Apr 8;19(1):74. doi: 10.1186/s13075-017-1280-6.
The efficacy and safety of direct-acting antiviral agents (DAAs) were evaluated in a cohort of prospectively enrolled patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC), an immune complex-mediated vasculitis of small and medium vessels in which the pathogenetic role of HCV has been clearly established.
Twenty-two patients received DAAs. Clinical and laboratory features were recorded at baseline, every 4 weeks until the end of treatment (EoT), and 12 weeks afterwards. Primary efficacy endpoints were (a) sustained virological response 12 weeks after therapy completion (SVR12), (b) regression of symptomatology (clinical response) and (c) cryoglobulin disappearance or cryocrit reduction ≥50% (immunological response). Complete response (CR) was defined as the occurrence of all three primary endpoints; partial response (PR) was defined as the occurrence of SVR12, with or without either immunological or clinical response; and no response was defined as missing the achievement of all three endpoints.
All patients reached SVR12. Compared with basal values, mean cryocrit values were significantly decreased at EoT and SVR12. A significant reduction of alanine transaminase and a parallel increase of complement component C4 levels were also detected. Rheumatoid factor activity was significantly reduced at EoT but not at SVR12. At SVR12, a CR was established in 14 patients (63.7%) and a PR in 8 patients (36.3%). In one patient with small lymphocytic lymphoma, the tumour progressed despite viral clearance. Mild adverse events were recorded in nine patients (40.9%).
The response rates induced by the use of DAAs in patients with MC were remarkably higher than those previously achieved with pegylated interferon-α/ribavirin, with or without rituximab. A much longer follow-up is desirable to achieve useful information in terms of persistent viral clearance and clinical response.
在一组前瞻性纳入的丙型肝炎病毒（HCV）相关混合性冷球蛋白血症（MC）患者中评估了直接抗病毒药物（DAA）的疗效和安全性。MC是一种免疫复合物介导的中小血管血管炎，其中HCV的致病作用已得到明确证实。
22例患者接受了DAA治疗。在基线、治疗结束（EoT）前每4周以及治疗结束后12周记录临床和实验室特征。主要疗效终点为：（a）治疗完成后12周持续病毒学应答（SVR12）；（b）症状消退（临床应答）；（c）冷球蛋白消失或冷沉淀比容降低≥50%（免疫应答）。完全缓解（CR）定义为所有三个主要终点均出现；部分缓解（PR）定义为出现SVR12，无论是否伴有免疫或临床应答；无应答定义为未达到所有三个终点。
所有患者均达到SVR12。与基线值相比，EoT和SVR12时平均冷沉淀比容值显著降低。还检测到丙氨酸转氨酶显著降低，补体成分C4水平平行升高。类风湿因子活性在EoT时显著降低，但在SVR12时未降低。在SVR12时，14例患者（63.7%）达到CR，8例患者（36.3%）达到PR。在1例小淋巴细胞淋巴瘤患者中，尽管病毒清除，但肿瘤仍进展。9例患者（40.9%）记录到轻度不良事件。
MC患者使用DAA诱导的应答率显著高于既往使用聚乙二醇化干扰素-α/利巴韦林（无论是否联合利妥昔单抗）所取得的应答率。需要更长时间的随访以获得关于持续病毒清除和临床应答方面的有用信息。
