Mazzaro C, Carniello G S, Colle R, Doretto P, Mazzi G, Crovatto M, Santini G F, Tulissi P, Gregoretti M, Mazzoran L, Russo A, Silvestri F, Pozzato G
First Department of Medicine, Pordenone General Hospital, Italy.
Ital J Gastroenterol Hepatol. 1997 Aug;29(4):343-50.
In a previous paper, we reported on the short-term efficacy of alpha-interferon in the treatment of hepatitis C virus positive mixed cryoglobulinaemia.
We investigated the long-term effects of therapy in a larger group of patients, and the viral and host factors able to influence the response to treatment.
In 27 females and 15 males (mean age 54.8 +/- 9.1 years) affected by mixed cryoglobulinaemia, bone marrow biopsy and phenotyping of marrow cells were performed before treatment and at the end of follow-up. A liver biopsy was obtained from patients showing biochemical signs of chronic liver disease. The presence of hepatitis C virus was assessed by detection of serum anti-hepatitis C virus antibodies, and hepatitis C virus-RNA. The treatment schedule was 3 million units of recombinant interferon alpha-2b three times a week for one year. Follow-up lasted for 1 year after the end of treatment. The response was classified as follows: 1) Complete response: Disappearance of the cryocrit (or reduction of more than 50%) and of all clinical manifestations of the disease. 2) Partial response: Disappearance of all clinical signs of the disease, but reduction of cryocrit of less than 50%. 3) Minor response: Reduction of cryocrit of less than 20% associated with the disappearance of one or more (but not all) signs of vasculitis.
Anti-hepatitis C virus antibodies were present in 41 (95%) patients, and hepatitis C virus-RNA was detectable in all cases. Before therapy, marrow histology showed a massive monomorphous infiltration by plasmacytoid lymphocytes indicating the presence of low-grade non-Hodgkin lymphoma in 7 cases (16.6%). After therapy, 13 (31%) patients achieved a complete response, 23 patients (55%) a partial response, and 6 patients (14%) a minor response. Seven of the responders and all patients showing partial or minor responses relapsed a few months after withdrawal of therapy. At the end of the follow-up, only 6 patients had obtained complete remission. Bone marrow examination showed that B-lymphocytic monoclonal infiltrate had disappeared in 3 long-term responders. No difference was found between responders and non-responders/relapsers in terms of age, sex, duration of the disease, severity of symptoms, liver function tests, rheumatoid factor or complement levels, while the lack of response was associated with the presence of genotype 1b, liver cirrhosis, and high cryoglobulin level.
Mixed cryoglobulinaemia is associated with a high prevalence of B-cell lymphomas. Alpha-Interferon is an effective agent for the treatment of this disease and seems able to determine regression of the lymphoproliferative disorder. The hepatitis C virus genotype and cryoglobulin level are the most important predictive factors of response to therapy.
在之前的一篇论文中，我们报道了α-干扰素治疗丙型肝炎病毒阳性混合性冷球蛋白血症的短期疗效。
我们在更大一组患者中研究了治疗的长期效果，以及能够影响治疗反应的病毒和宿主因素。
对27名女性和15名男性（平均年龄54.8±9.1岁）混合性冷球蛋白血症患者，在治疗前和随访结束时进行骨髓活检及骨髓细胞表型分析。对有慢性肝病生化指标的患者进行肝活检。通过检测血清抗丙型肝炎病毒抗体和丙型肝炎病毒RNA评估丙型肝炎病毒的存在情况。治疗方案为重组干扰素α-2b 300万单位，每周3次，共1年。治疗结束后随访1年。反应分类如下：1）完全缓解：冷球蛋白血症（或降低超过50%）及疾病所有临床表现消失。2）部分缓解：疾病所有临床体征消失，但冷球蛋白血症降低少于50%。3）轻微缓解：冷球蛋白血症降低少于20%，伴有一种或多种（但非全部）血管炎体征消失。
41名（95%）患者存在抗丙型肝炎病毒抗体，所有病例均检测到丙型肝炎病毒RNA。治疗前，骨髓组织学显示浆细胞样淋巴细胞大量单形浸润，7例（16.6%）提示存在低度非霍奇金淋巴瘤。治疗后，13名（31%）患者达到完全缓解，23名（55%）患者部分缓解，6名（14%）患者轻微缓解。7名缓解者及所有部分或轻微缓解患者在治疗停药后数月复发。随访结束时，仅6名患者获得完全缓解。骨髓检查显示3名长期缓解者的B淋巴细胞单克隆浸润消失。在年龄、性别、病程、症状严重程度、肝功能检查、类风湿因子或补体水平方面，缓解者与未缓解者/复发者之间未发现差异，而无反应与1b型基因型、肝硬化及高冷球蛋白水平有关。
混合性冷球蛋白血症与B细胞淋巴瘤的高患病率相关。α-干扰素是治疗该疾病的有效药物，似乎能够使淋巴增殖性疾病消退。丙型肝炎病毒基因型和冷球蛋白水平是治疗反应的最重要预测因素。
