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利巴韦林治疗肝移植受者慢性戊型肝炎病毒感染。

Ribavirin for chronic hepatitis E virus infection in transplant recipients.

机构信息

The authors' affiliations are listed in the Appendix.

出版信息

N Engl J Med. 2014 Mar 20;370(12):1111-20. doi: 10.1056/NEJMoa1215246.

Abstract

BACKGROUND

There is no established therapy for hepatitis E virus (HEV) infection. The aim of this retrospective, multicenter case series was to assess the effects of ribavirin as monotherapy for solid-organ transplant recipients with prolonged HEV viremia.

METHODS

We examined the records of 59 patients who had received a solid-organ transplant (37 kidney-transplant recipients, 10 liver-transplant recipients, 5 heart-transplant recipients, 5 kidney and pancreas-transplant recipients, and 2 lung-transplant recipients). Ribavirin therapy was initiated a median of 9 months (range, 1 to 82) after the diagnosis of HEV infection at a median dose of 600 mg per day (range, 29 to 1200), which was equivalent to 8.1 mg per kilogram of body weight per day (range, 0.6 to 16.3). Patients received ribavirin for a median of 3 months (range, 1 to 18); 66% of the patients received ribavirin for 3 months or less.

RESULTS

All the patients had HEV viremia when ribavirin was initiated (all 54 in whom genotyping was performed had HEV genotype 3). At the end of therapy, HEV clearance was observed in 95% of the patients. A recurrence of HEV replication occurred in 10 patients after ribavirin was stopped. A sustained virologic response, defined as an undetectable serum HEV RNA level at least 6 months after cessation of ribavirin therapy, occurred in 46 of the 59 patients (78%). A sustained virologic response was also observed in 4 patients who had a recurrence and were re-treated for a longer period. A higher lymphocyte count when ribavirin therapy was initiated was associated with a greater likelihood of a sustained virologic response. Anemia was the main identified side effect and required a reduction in ribavirin dose in 29% of the patients, the use of erythropoietin in 54%, and blood transfusions in 12%.

CONCLUSIONS

This retrospective, multicenter study showed that ribavirin as monotherapy may be effective in the treatment of chronic HEV infection; a 3-month course seemed to be an appropriate duration of therapy for most patients.

摘要

背景

目前针对戊型肝炎病毒(HEV)感染还没有确立的治疗方法。本回顾性多中心病例系列研究的目的是评估利巴韦林单药治疗持续性 HEV 病毒血症的实体器官移植受者的效果。

方法

我们对 59 名接受过实体器官移植(37 名肾移植受者、10 名肝移植受者、5 名心脏移植受者、5 名肾和胰腺移植受者、2 名肺移植受者)的患者的记录进行了检查。在诊断 HEV 感染后中位数 9 个月(范围 1 至 82 个月)开始给予利巴韦林治疗,中位数剂量为每天 600 毫克(范围 29 至 1200 毫克),相当于每天 8.1 毫克/公斤体重(范围 0.6 至 16.3)。患者接受利巴韦林治疗的中位数时间为 3 个月(范围 1 至 18 个月);66%的患者接受利巴韦林治疗时间不足 3 个月。

结果

所有患者在开始使用利巴韦林时均有 HEV 病毒血症(所有 54 例进行基因分型的患者均为 HEV 基因型 3)。治疗结束时,95%的患者 HEV 清除。利巴韦林停药后 10 例患者出现 HEV 复制复发。在停止利巴韦林治疗至少 6 个月后血清 HEV RNA 水平无法检测到的持续病毒学应答定义为 59 例患者中的 46 例(78%)。4 例复发并延长治疗时间的患者也观察到持续病毒学应答。利巴韦林治疗开始时淋巴细胞计数较高与持续病毒学应答的可能性更大相关。贫血是主要的不良反应,需要减少 29%的患者的利巴韦林剂量,54%的患者使用促红细胞生成素,12%的患者输血。

结论

这项回顾性多中心研究表明,利巴韦林单药治疗可能对慢性 HEV 感染有效;3 个月的疗程似乎对大多数患者是适当的治疗时间。

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