Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses MASVE, University of Florence, Florence, Italy.
J Transl Med. 2014 Jan 24;12:21. doi: 10.1186/1479-5876-12-21.
Mixed cryoglobulinemia (MC) is a HCV-related lymphoproliferative disorder generally associated with advanced liver disease. Liver stiffness has been significantly correlated with histopathological stage of fibrosis. Moreover, it was influenced by necroinflammatory activity. Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody inducing transient B lymphocytes depletion that was shown to be useful and safe in the majority of HCV MC patients, leading also to improvement of cirrhotic syndrome. Aim of this study was to evaluate the modifications of liver stiffness following RTX treatment in HCV-related MC patients.
Fourteen consecutive patients (10 F, 4 M; mean age 60.43 ± 43) with HCV-related chronic hepatitis (n = 10) or cirrhosis (n = 4) and MC, eligible for RTX treatment, were prospectively enrolled. Intravenous injection of 1 g of RTX was performed at day 0 and at day 15. Assessment of stiffness was carried out by Fibroscan (Echosens, Paris-France) at baseline, 15 days after the first infusion, and at month 1, 3 and 6 after therapy.
MC symptoms significantly improved during the study, especially during the first 3 months. Liver stiffness observed 3 months after treatment was significantly reduced when compared with pre-treatment values (p = 0.01). This difference disappeared after 6 months of follow-up. Cytofluorimetric analysis showed a decrease of CD19+ peripheral blood cells, with the nadir at month 3 after therapy and B cell compartment reconstitution after 6 months.
This study, for the first time showed that RTX-treatment in HCV-related MC induces a reduction of liver stiffness that is strictly associated with the B-cell depletion.
混合性冷球蛋白血症(MC)是一种与丙型肝炎病毒(HCV)相关的淋巴增生性疾病,通常与晚期肝病有关。肝脏硬度与纤维化的组织病理学分期有显著相关性。此外,它还受到坏死性炎症活动的影响。利妥昔单抗(RTX)是一种嵌合抗 CD20 单克隆抗体,可诱导 B 淋巴细胞短暂耗竭,已被证明在大多数 HCV-MC 患者中安全且有效,还可改善肝硬化综合征。本研究旨在评估 RTX 治疗 HCV 相关 MC 患者后肝脏硬度的变化。
14 例连续的 HCV 相关慢性肝炎(n=10)或肝硬化(n=4)和 MC 患者,符合 RTX 治疗条件,前瞻性纳入本研究。在第 0 天和第 15 天静脉注射 1g 的 RTX。在基线、第一次输注后 15 天、治疗后 1、3 和 6 个月通过 Fibroscan(Echosens,巴黎,法国)评估硬度。
在研究期间,MC 症状显著改善,尤其是在前 3 个月。与治疗前相比,治疗 3 个月后的肝脏硬度明显降低(p=0.01)。这种差异在 6 个月的随访后消失。流式细胞术分析显示外周血 CD19+细胞减少,最低值出现在治疗后 3 个月,6 个月后 B 细胞重建。
本研究首次表明,RTX 治疗 HCV 相关 MC 可降低肝脏硬度,与 B 细胞耗竭密切相关。