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聚乙二醇化干扰素和利巴韦林治疗血液透析患者的丙型肝炎

Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients.

作者信息

Bruchfeld A, Lindahl K, Reichard O, Carlsson T, Schvarcz R

机构信息

Department of Renal Medicine, Karolinska University Hospital Huddinge and Solna, Karolinska Institute, Stockholm, Sweden.

出版信息

J Viral Hepat. 2006 May;13(5):316-21. doi: 10.1111/j.1365-2893.2005.00680.x.

Abstract

Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for 24-48 weeks according to genotype with a dose of 50 or 135 mug/week respectively. All patients were given reduced ribavirin doses, initially 200-400 mg/day. Ribavirin trough plasma concentrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10-15 micromol/L. Interferon related side-effects were common, in one patient peg-alfa-2b was permanently reduced to 50 mug every 9-10 days with improvement in tolerance. Average ribavirin dose was 170-300 mg/day. Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR negative during treatment which was completed or nearly completed in four patients. One patient terminated therapy prematurely due to pronounced interferon related side-effects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant. Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the pharmacokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made.

摘要

慢性丙型肝炎(HCV)的标准治疗方法是聚乙二醇化干扰素联合利巴韦林。这两种药物在透析患者(终末期肾病,ESRD)中的使用经验有限。6例血液透析患者,4例为HCV 1型,1例为4型,1例为2型,根据基因型分别使用聚乙二醇化干扰素-α-2b(n = 4)和聚乙二醇化干扰素-α-2a(n = 2)治疗24 - 48周,剂量分别为50或135μg/周。所有患者均给予减量的利巴韦林,初始剂量为200 - 400mg/天。采用先前为早期治疗研究开发的高效液相色谱法测定利巴韦林的血浆谷浓度,目标浓度为10 - 15μmol/L。干扰素相关的副作用很常见,1例患者聚乙二醇化干扰素-α-2b剂量永久性减至每9 - 10天50μg,耐受性有所改善。利巴韦林的平均剂量为170 - 300mg/天。利巴韦林引起的贫血采用大剂量促红细胞生成素和小剂量铁剂治疗。无需输血。所有患者在治疗期间HCV - RNA - PCR均转为阴性,4例患者完成或接近完成治疗。1例患者因明显的干扰素相关副作用提前终止治疗,另1例死于心肌梗死,可能与治疗无关。3例患者在延长随访期内HCV - RNA仍为阴性,其中2例成功进行了肾移植。聚乙二醇化干扰素可能会成为ESRD患者HCV治疗的一种有价值的补充药物,并且有可能与利巴韦林联合使用。然而,在做出明确的给药建议之前,需要在前瞻性研究中更密切地研究聚乙二醇化干扰素-α-2a和2b的药代动力学和耐受性。

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