Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy
Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy
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DOI：
10.1128/aac.02496-15
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发表时间：
2016-03-01
影响因子：
4.9
通讯作者：
Izopet, Jacques
中科院分区：
文献类型：
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作者：
Lhomme, Sebastien;Kamar, Nassim;Izopet, Jacques
戊型肝炎病毒（HEV）可导致实体器官移植患者的慢性感染。利巴韦林对治疗慢性感染患者有效。最近，HEV聚合酶中的1634 R突变与治疗失败有关。然而，目前还不清楚这种突变是否可以作为治疗结果的预后标志物。我们研究了开始利巴韦林治疗的患者中HEV聚合酶1634 R突变的患病率、1634 R变异对病毒应答的影响、治疗失败的患者中1634 R突变的频率及其对利巴韦林再治疗的影响。我们使用深度测序分析了63例慢性戊型肝炎实体器官移植患者的预处理样本; 42例患者有持续病毒学应答（SVR），21例是非SVR患者。我们通过深度测序在36.5%（23/63）的患者中检测到1634 R变异（比例为1.3至100%）。在SVR患者的基线血浆样本中检测到31.0%（13/42）的1634 R变异体，在其他患者中检测到47.6%（10/21）的1634 R变异体（P = 0.2）。该突变的存在不影响病毒RNA的初始减少。最后，第二次延长利巴韦林治疗导致70%最初没有SVR的患者发生SVR，尽管存在1634 R变异。我们的结论是，在利巴韦林启动1634 R变异的存在下，不会导致绝对的利巴韦林耐药。尽管在治疗失败的患者中其比例增加，但1634 R变异的存在并不影响对第二次利巴韦林治疗的反应。
Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the 1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.