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替诺福韦艾拉酚胺作为一名患有范科尼综合征和多药耐药病史的乙肝肝硬化患者的挽救治疗药物。

Tenofovir alafenamide as a rescue therapy in a patient with HBV-cirrhosis with a history of Fanconi syndrome and multidrug resistance.

作者信息

Grossi Glenda, Loglio Alessandro, Facchetti Floriana, Borghi Marta, Soffredini Roberta, Galmozzi Enrico, Lunghi Giovanna, Gaggar Anuj, Lampertico Pietro

机构信息

"A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.

Virology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.

出版信息

J Hepatol. 2017 Sep 21. doi: 10.1016/j.jhep.2017.08.020.

DOI:10.1016/j.jhep.2017.08.020
PMID:28870666
Abstract

Tenofovir disoproxil fumarate (TDF) is a recommended first-line therapy for both naïve and experienced patients with chronic hepatitis B (CHB), although reduced estimated glomerular filtration rate (eGFR), hypophosphatemia, hyperphosphaturia and Fanconi syndrome have been reported in some patients. Entecavir (ETV) could be considered as a rescue therapy for TDF-treated patients developing renal dysfunction, though patients with prior history of treatment with lamivudine (LAM) can develop ETV resistance strains, which can lead to potentially severe hepatitis flares. Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has recently been developed to improve the renal and bone safety profile compared to TDF, while maintaining the same virologic efficacy. The recently published 48-week phase III TAF registration studies confirmed the superior safety profile. Here we describe a case of a 75-year-old woman with HBV mono-infection and compensated cirrhosis who developed ETV resistant strains and grade 3 chronic kidney disease after many years of LAM and adefovir (ADV) treatment and a TDF-induced Fanconi syndrome. The administration of 25mg/day of TAF, granted as part of a compassionate use program, rapidly suppressed viral replication to undetectable levels without worsening renal function or side effects.

摘要

替诺福韦酯(TDF)是初治和经治慢性乙型肝炎(CHB)患者推荐的一线治疗药物,不过有部分患者报告出现了估算肾小球滤过率(eGFR)降低、低磷血症、高磷尿症和范科尼综合征。对于接受TDF治疗出现肾功能不全的患者,恩替卡韦(ETV)可作为挽救治疗药物,不过有拉米夫定(LAM)治疗史的患者可能会产生ETV耐药株,这可能导致潜在的严重肝炎发作。替诺福韦艾拉酚胺(TAF)是替诺福韦的一种新前体药物,与TDF相比,最近已开发出来以改善肾脏和骨骼安全性,同时保持相同的病毒学疗效。最近发表的48周III期TAF注册研究证实了其卓越的安全性。在此,我们描述了一例75岁女性,患有HBV单一感染且肝硬化代偿,在接受多年LAM和阿德福韦(ADV)治疗以及TDF诱导的范科尼综合征后,出现了ETV耐药株和3级慢性肾脏病。作为同情用药计划的一部分,给予每日25mg的TAF治疗后,病毒复制迅速被抑制到检测不到的水平,且肾功能未恶化,也未出现副作用。

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引用本文的文献

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J Clin Transl Hepatol. 2023 Nov 28;11(6):1425-1442. doi: 10.14218/JCTH.2023.00320. Epub 2023 Aug 15.
2
Fanconi syndrome induced by the long-term use of tenofovir disoproxil fumarate: a case report and literature review.富马酸替诺福韦二吡呋酯长期使用导致范可尼综合征:病例报告及文献复习。
J Int Med Res. 2023 Aug;51(8):3000605231195469. doi: 10.1177/03000605231195469.
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Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada.
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Can Liver J. 2018 Dec 25;1(4):156-217. doi: 10.3138/canlivj.2018-0008. eCollection 2018 Fall.
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The comparison of different antiviral therapies on the prognosis of hepatitis B virus-related hepatocellular carcinoma after curative treatments: A network meta-analysis.不同抗病毒治疗对根治性治疗后乙型肝炎病毒相关肝细胞癌预后的比较:一项网状Meta分析。
Medicine (Baltimore). 2020 Aug 14;99(33):e20877. doi: 10.1097/MD.0000000000020877.
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Comparative efficacy of the front-line anti-HBV drugs in nucleos(t)ide analogue-naive chronic hepatitis B: A protocol for systematic review and network meta-analysis.初治慢性乙型肝炎患者一线抗乙肝病毒药物的比较疗效:系统评价与网状Meta分析方案
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