干扰素和利巴韦林治疗丙型肝炎相关肾病及肾功能不全患者。

Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency.

作者信息

Bruchfeld Annette, Lindahl Karin, Ståhle Lars, Söderberg Magnus, Schvarcz Robert

机构信息

Division of Renal Medicine, Department of Clinical Science, Karolinska Institute and Huddinge University Hospital, S-141 86 Stockholm, Sweden.

出版信息

Nephrol Dial Transplant. 2003 Aug;18(8):1573-80. doi: 10.1093/ndt/gfg209.

DOI:10.1093/ndt/gfg209

PMID:12897097

Abstract

BACKGROUND

Hepatitis C virus (HCV) infection is associated with renal manifestations, such as membranoproliferative glomerulonephritis (MPGN) with or without cryoglobulinaemia, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS). Standard treatment for HCV is interferon and ribavirin, but in renal insufficiency ribavirin has been contraindicated due to fear of side effects.

METHODS

Seven patients, two with cryoglobulinaemia, vasculitic manifestations and glomerulonephritis (GN), four with MPGN and one with FSGS were treated with a combination of interferon and ribavirin. Two patients were given pegylated interferon and ribavirin. All patients had at presentation renal insufficiency, with a glomerular filtration rate (GFR) between 10 and 65 ml/min. One patient had HCV genotype 1, the remainder 2 and 3. Duration of therapy was according to genotype (6-12 months). Ribavirin in plasma was monitored by high-performance liquid chromatography (HPLC) to avoid over-dosing, aiming at a target concentration of 10-15 micromol/l. The main side effect of ribavirin, haemolytic anaemia, was monitored closely with haemoglobin controls.

RESULTS

Six of seven patients became HCV-RNA-PCR negative and four of seven have maintained both virological and renal remission. One of seven has maintained virological and partial renal remission. One patient did not tolerate interferon, but is in renal remission with low-dose ribavirin. One vasculitis patient responded with complete remission, but relapsed virologically and had a minor vasculitic flare after 9 months. Only one patient with vasculitis had low-dose immunosuppression in addition to anti-viral therapy. Average daily ribavirin dose was 200-800 mg. Ribavirin-induced anaemia was managed in five of seven patients with low-dose iron and erythropoietin between 4000 and 20 000 IU/week.

CONCLUSIONS

Interferon and ribavirin can with reasonable safety be used in HCV-related vasculitis and GN irrespective of renal function.

摘要

背景

丙型肝炎病毒（HCV）感染与肾脏表现相关，如伴有或不伴有冷球蛋白血症的膜增生性肾小球肾炎（MPGN）、膜性肾小球肾炎（MGN）和局灶节段性肾小球硬化（FSGS）。HCV的标准治疗方法是干扰素和利巴韦林，但在肾功能不全的情况下，由于担心副作用，利巴韦林一直被列为禁忌。

方法

7例患者接受了干扰素和利巴韦林联合治疗，其中2例伴有冷球蛋白血症、血管炎表现和肾小球肾炎（GN），4例患有MPGN，1例患有FSGS。2例患者接受了聚乙二醇化干扰素和利巴韦林治疗。所有患者就诊时均存在肾功能不全，肾小球滤过率（GFR）在10至65ml/分钟之间。1例患者为HCV基因1型，其余为2型和3型。治疗持续时间根据基因型而定（6至12个月）。通过高效液相色谱（HPLC）监测血浆中的利巴韦林，以避免过量给药，目标浓度为10至15微摩尔/升。密切监测利巴韦林的主要副作用溶血性贫血，定期检测血红蛋白。

结果

7例患者中有6例HCV-RNA-PCR检测呈阴性，7例中有4例维持了病毒学缓解和肾脏缓解。7例中有1例维持了病毒学缓解和部分肾脏缓解。1例患者不耐受干扰素，但低剂量利巴韦林治疗后肾脏缓解。1例血管炎患者完全缓解，但9个月后病毒学复发并出现轻微血管炎发作。只有1例血管炎患者在抗病毒治疗的基础上接受了低剂量免疫抑制治疗。利巴韦林的平均每日剂量为200至800毫克。7例患者中有5例通过低剂量铁剂和每周4000至20000国际单位的促红细胞生成素治疗利巴韦林引起的贫血。