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多发性骨髓瘤患者的戊型肝炎病毒感染:免疫治疗时代的新挑战

英文原题:Hepatitis E virus infections in people with multiple myeloma: an emerging challenge in the era of immunotherapeutic approaches.

查看英文原题

Hepatitis E virus infections in people with multiple myeloma: an emerging challenge in the era of immunotherapeutic approaches.

PubMed 2025/09/25(内容时间) Haematologica Q1 · IF 8.2(JCR 2025)

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中文摘要

戊型肝炎病毒(HEV)是尚未得到充分认识的病毒性肝炎病因;高收入国家的发病率正在上升,主要由人畜共患传播所致。多发性骨髓瘤(MM)患者尤其容易感染HEV,但目前尚无抗病毒治疗建议,也不清楚HEV对骨髓瘤治疗管理的影响。本文报告西欧一家三级医疗中心在不到一年内诊断的7例MM合并HEV感染患者(男性5例、女性2例)。所有病例的外周血HEV RNA PCR检测均为阳性。虽然未发生暴发性肝炎,HEV感染仍导致临床上重要的治疗中断:自体干细胞移植延期、CAR-T 制备用淋巴细胞单采延迟,双特异性抗体方案暂停最长达5个月。4例患者开始接受利巴韦林治疗。3例接受T细胞重定向治疗的患者(其中1例此前接受西达基奥仑赛治疗,2例接受双特异性抗体治疗)尽管使用利巴韦林,仍进展为慢性感染。一名患者虽然外周血HEV已清除,却出现持续眩晕,脑脊液HEV RNA检测阳性,提示病毒侵入神经系统。作为目前报告中规模最大的MM合并HEV感染队列,也是首个记录T细胞重定向治疗期间慢性感染的研究,本研究强调:亟需提高对HEV这一新兴威胁的认识;完善基线筛查及原因不明转氨酶升高时的筛查方案;并在新型免疫治疗时代建立标准化治疗策略。

展开英文摘要原文

Hepatitis E virus (HEV) is an under-recognized cause of viral hepatitis, with rising incidence in high-income countries largely driven by zoonotic transmission. Patients with multiple myeloma (MM) are especially vulnerable to HEV, yet there have been no recommendations for antiviral treatment or on its impact on the management of myeloma treatment.

Here, we describe 7 patients (5 males, 2 females) with MM who were diagnosed with HEV infection at a tertiary care center in Western Europe within less than one year. All cases were confirmed by positive HEV RNA PCR in peripheral blood. Although no instances of fulminant hepatitis were observed, HEV prompted clinically relevant interruptions: autologous stem cell transplantation was postponed, lymphocyte apheresis for CAR T-cell manufacturing was delayed, and bispecific antibody regimens were suspended for up to five months. Ribavirin was initiated in 4 cases. The 3 patients undergoing T-cell-redirecting therapies, including one with prior ciltacabtagene autoleucel and 2 on bispecific antibodies, progressed to chronic infection despite ribavirin treatment.

One patient, despite clearing HEV from peripheral blood, developed persistent vertigo and tested positive for HEV RNA in cerebrospinal fluid, indicating neuroinvasion.

As the largest reported cohort of MM patients with HEV infections and the first to document chronic infection during treatment with T-cell-redirecting therapies, this study emphasizes the urgent need to increase awareness of HEV as an emerging threat, refine screening protocols at baseline or during unexplained aminotransferase flares, and to establish standardized therapeutic strategies in the era of novel immunotherapeutic approaches.

论文信息

作者
Al-Bazaz M、Pischke S、Alsdorf W、Sonnemann P、Cichutek S、Wiesch JSZ、Schaefers C、Artzenroth J
第一作者单位
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20251 Hamburg.Germany
通讯作者单位
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20251 Hamburg. r.kosch@uke.de.Germany
文献类型
非美国政府资助研究
期刊
Haematologica2026 Mar 1
原文标识
PubMed 40994343 · DOI 10.3324/haematol.2025.288381