Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Internal Medicine, University of Florence, Florence, Italy.
Blood. 2010 Jul 22;116(3):335-42. doi: 10.1182/blood-2009-11-253948. Epub 2010 Mar 22.
The effectiveness of rituximab in hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC) has been shown. However, the risk of an increase in viral replication limits its use in cirrhosis, a condition frequently observed in patients with MC. In this prospective study, 19 HCV-positive patients with MC and advanced liver disease, who were excluded from antiviral therapy, were treated with rituximab and followed for 6 months. MC symptoms included purpura, arthralgias, weakness, sensory-motor polyneuropathy, nephropathy, and leg ulcers. Liver cirrhosis was observed in 15 of 19 patients, with ascitic decompensation in 6 cases. A consistent improvement in MC syndrome was evident at the end-of-treatment (EOT) and end-of-follow-up (EOF-U). Variable modifications in both mean viral titers and alanine aminotransferase values were observed at admission, EOT, third month of follow-up, and EOF-U (2.62 x 10(6), 4.28 x 10(6), 4.82 x 10(6), and 2.02 x 10(6) IU/mL and 63.6, 49.1, 56.6, and 51.4 IU/L, respectively). Improvement in liver protidosynthetic activity and ascites degree was observed at EOT and EOF-U, especially in more advanced cases. This study shows the effectiveness and safety of rituximab in MC syndrome with advanced liver disease. Moreover, the depletion of CD20(+) B cells was also followed by cirrhosis syndrome improvement despite the possibility of transient increases of viremia titers.
利妥昔单抗已被证明对丙型肝炎病毒（HCV）相关混合性冷球蛋白血症（MC）有效。然而，病毒复制增加的风险限制了其在肝硬化中的应用，而肝硬化在 MC 患者中很常见。在这项前瞻性研究中，19 例 HCV 阳性、有进展性肝病且被排除抗病毒治疗的 MC 患者接受了利妥昔单抗治疗，并随访了 6 个月。MC 症状包括紫癜、关节痛、乏力、感觉运动性多发性神经病、肾病和腿部溃疡。19 例患者中有 15 例存在肝硬化，6 例出现腹水失代偿。在治疗结束时（EOT）和随访结束时（EOF-U），MC 综合征明显改善。入院时、EOT、随访第 3 个月和 EOF-U 时，平均病毒滴度和丙氨酸氨基转移酶值均有不同程度的变化（2.62×10(6)、4.28×10(6)、4.82×10(6)和 2.02×10(6)IU/mL 和 63.6、49.1、56.6 和 51.4 IU/L）。EOT 和 EOF-U 时观察到肝脏蛋白合成活性和腹水程度的改善，尤其是在更严重的病例中。这项研究表明，利妥昔单抗在伴有进展性肝病的 MC 综合征中是有效且安全的。此外，尽管病毒载量可能暂时增加，但 CD20(+)B 细胞耗竭也会改善肝硬化综合征。
