Grossi Glenda, Loglio Alessandro, Facchetti Floriana, Borghi Marta, Soffredini Roberta, Galmozzi Enrico, Lunghi Giovanna, Gaggar Anuj, Lampertico Pietro
"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.
J Hepatol. 2017 Sep 21. doi: 10.1016/j.jhep.2017.08.020.
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.
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。