Zuckerman E, Keren D, Slobodin G, Rosner I, Rozenbaum M, Toubi E, Sabo E, Tsykounov I, Naschitz J E, Yeshurun D
Liver Clinic, Department of Internal Medicine A, B'nai Zion Medical Center, Bruce Rappaport Faculty of Medicine, Technion, Israel.
J Rheumatol. 2000 Sep;27(9):2172-8.
To assess the benefit of interferon-alpha/ribavirin combination therapy in hepatitis C virus (HCV) infected patients with symptomatic mixed cryoglobulinemia (MC) who failed to respond to treatment with interferon-alpha (IFN-alpha).
Nine patients (mean age 57 +/- 14 yrs) with type II symptomatic MC who failed to respond to IFN-alpha monotherapy were re-treated with combination treatment of IFN-alpha 3 times weekly and ribavirin 15 mg/kg daily for 6 months. Five of 9 patients had previously received additional treatment during IFN-alpha monotherapy. Clinical and laboratory evaluations (including cryocrit level) were performed weekly for the first month and monthly thereafter.
Baseline mean alanine aminotransferase (ALT) and cryocrit levels were 119 +/- 97 IU/l and 7.9% +/- 10%, respectively. All patients were HCV-RNA positive and 5 had cirrhosis. At the end of therapy, mean ALT level was 84 +/- 79 IU/l (p = 0.02), while normal ALT levels were observed in 4 of 9 patients (44%). However, complete virological response was achieved in only 2 patients (22%). Cryoglobulin became undetectable within 6 weeks of therapy in 7 patients (78%) and decreased significantly in 2 others (p = 0.008). A substantial improvement in MC related symptoms (arthralgia/arthritis, proteinuria, skin vasculitis) was achieved in all patients within 10 weeks of combination therapy, although polyneuropathy related symptoms were relatively resistant to treatment.
Symptomatic, refractory HCV related MC should be considered as an indication for combination therapy with IFN-alpha and ribavirin. Improvement in MC related symptoms can be achieved even without complete biochemical or virological response.
评估α干扰素/利巴韦林联合治疗对丙型肝炎病毒（HCV）感染的有症状混合性冷球蛋白血症（MC）患者的疗效，这些患者对α干扰素治疗无反应。
9例（平均年龄57±14岁）II型有症状MC患者，对α干扰素单一疗法无反应，接受每周3次α干扰素联合利巴韦林15mg/kg每日治疗，共6个月。9例患者中有5例在α干扰素单一疗法期间曾接受过其他治疗。在第一个月每周进行临床和实验室评估（包括冷球蛋白水平），此后每月评估一次。
基线时平均丙氨酸转氨酶（ALT）和冷球蛋白水平分别为119±97IU/L和7.9%±10%。所有患者HCV-RNA均为阳性，5例有肝硬化。治疗结束时，平均ALT水平为84±79IU/L（p=0.02），9例患者中有4例（44%）ALT水平正常。然而，仅2例患者（22%）实现了完全病毒学应答。7例患者（78%）在治疗6周内冷球蛋白检测不到，另外2例患者冷球蛋白显著下降（p=0.008）。联合治疗10周内所有患者与MC相关的症状（关节痛/关节炎、蛋白尿、皮肤血管炎）均有显著改善，尽管与多发性神经病相关的症状对治疗相对耐药。
有症状的、难治性HCV相关MC应被视为α干扰素和利巴韦林联合治疗的适应证。即使没有完全的生化或病毒学应答，与MC相关的症状也可得到改善。
