AASLD2014:恩替成功救出替诺导范可尼综合征

StephenW

1908
Tenofovir-Induced Fanconi Syndrome In Chronic Hepatitis B Monoinfected Patients Successfully Rescued By Entecavir


Mauro Vigand2, Alessandra Brocchieri3, Angiola Spinetti4, Serena Zaltron4, Giampaolo Mangia1, Floriana Facchetti1, Alessandro Fugazza3, Francesco Castelli4, Massimo Colombo1, Pietro Lamper-tico1;1Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy; 2Liver Unit, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy; 3Medicine Unit, Ospedale Maggiore di Lodi, Lodi, Italy; 4University Division of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Brescia, Italy

Despite the excellent safety records of tenofovir disoproxil fumarate (TDF), a few cases of Fanconi syndrome have been reported among human immunodeficiency virus (HIV) positive patients, and recently two cases of TDF-associated Fanconi syndrome have been reported in chronic hepatitis B (CHB) patients from Australia. Here, we describe two additional CHB patients who developed a Fanconi syndrome. A 68 year-old CHB male who had been previously exposed to adefovir dipivoxil (ADV) for 2 years, but without risk factors for renal dysfunction and normal baseline renal function, developed an increased serum creatinine (1.32 mg/dL, eGFR 57 mL/ min/1.73m2), hypophosphatemia (2.1 mg/dL), normoglycemic glycosuria and proteinuria indicative for Fanconi syndrome after 42 months of TDF. By switching TDF to entecavir (ETV), glomerular and tubular function rapidly normalized while serum HBV DNA remained undetectable during the subsequent 15 months of ETV treatment. The second was a 67-year-old CHB NUC naïve male with arterial hypertension under pharmacological control and normal renal function who developed a Fanconi syndrome (serum creatinine 3.35 mg/dL, eGFR 18 mL/min/1.73m2, hypophosphatemia 1.7 mg/dL, proteinuria and normoglycemic glycosuria) after 45 months of TDF administration. Following TDF withdrawal and ETV start, glomerular and tubular function progressively improved and serum HBV DNA remained persistently undetectable. Both patients were homozygous for the C allele at position -24 in the ABCC2 gene (rs717620 of MRP2), a polymorphism which has been associated with the genetic predisposition to accumulate TDF within tubular cells. In conclusion, though the overall risk of TDF associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular function should be carefully monitored in patients exposed to TDF, especially when other renal risk factors such as arterial hypertension, history of previous exposure to ADV or older age, are present. Proactive dose reductions of TDF may prevent the development of severe renal complications.

Disclosures:
Mauro Vigano - Consulting: Roche; Speaking and Teaching: Gilead Sciences, BMS
Serena Zaltron - Speaking and Teaching: BMS, MSD
Francesco Castelli - Grant/Research Support: Astellas, Pfizer, Abbott; Independent Contractor: BMS, Boheringer Ingheleim, ViiV, Schering, Roche, Janssen Cilag, Novartis
Massimo Colombo - Advisory Committees or Review Panels: BRISTOL-MEY-ERS-SQUIBB, SCHERING-PLOUGH, ROCHE, GILEAD, BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH, ROCHE, GILEAD, Janssen Cilag, Achillion; Grant/ Research Support: BRISTOL-MEYERS-SQUIBB, ROCHE, GILEAD, BRISTOL-MEY-ERS-SQUIBB, ROCHE, GILEAD; Speaking and Teaching: Glaxo Smith-Kline, BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH, ROCHE, NOVARTIS, GILEAD, VERTEX, Glaxo Smith-Kline, BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH, ROCHE, NOVARTIS, GILEAD, VERTEX, Sanofi
Pietro Lampertico - Advisory Committees or Review Panels: Bayer, Bayer; Speaking and Teaching: Bristol-Myers Squibb, Roche, GlaxoSmithKline, Novartis, Gilead, Bristol-Myers Squibb, Roche, GlaxoSmithKline, Novartis, Gilead
The following people have nothing to disclose: Alessandra Brocchieri, Angiola Spinetti, Giampaolo Mangia, Floriana Facchetti, Alessandro Fugazza

StephenW

1908
替诺福韦诱导范可尼综合征在慢性乙型肝炎单感染者成功救出恩替卡韦
毛罗Vigand2，亚历山德拉Brocchieri3，Angiola Spinetti4，小威Zaltron4，詹保罗Mangia1，弗洛里亚纳Facchetti1，亚历山德罗Fugazza3，弗朗西斯Castelli4，马西莫Colombo1，彼得Lamper-tico1;
1区胃肠病学和肝病基金会IRCCS钙“格兰达Ospedale教堂位于Policlinico工艺学院，米兰，米兰，意大利; 2Liver单位，Ospedale圣朱塞佩如Università德利阿布鲁Studi住宅米兰，米兰，意大利; 3Medicine单位，Ospedale焦雷迪洛迪，洛迪，意大利;传染病和热带病，布雷西亚和布雷西亚Spedali Civili总医院的大学，布雷西亚，意大利4University科

尽管富马酸替诺福韦酯（TDF）优异的安全记录，Fanconi综合征少数病例报告阳性的病人中人类免疫缺陷病毒（HIV），最近两例TDF相关Fanconi综合征已报告在慢性乙型肝炎（ CHB）患者来自澳大利亚。在这里，我们描述了两个额外的慢性乙肝患者谁开发了Fanconi综合征。一名68岁的男性的CHB谁已经预先暴露于阿德福韦酯（ADV）为2年，但没有危险因素的肾功能障碍和正常基线肾功能，开发了一种增加的血清肌酸酐（1.32毫克/升，表皮生长因子受体57毫升/分/1.73平方米），低磷（2.1毫克/分升），血糖正常性糖尿，蛋白尿指示42个月TDF后，范可尼综合征。通过切换TDF恩替卡韦（ETV），肾小球和肾小管功能迅速恢复正常，而血清HBV DNA在ETV治疗的随后15个月保持检测不到。第二个是一个67岁的慢性乙型肝炎NUC天真的男性，在药物的控制和肾功能正常的高血压谁开发了Fanconi综合征（血清肌酐3.35毫克/升，EGFR18毫升/分钟/1.73平方米，低磷血症1.7毫克/分升45个月TDF给药后，蛋白尿和糖尿血糖正常）。继撤出TDF和ETV开始，肾小球和肾小管功能的逐步完善和血清HBV DNA仍持续检测不到。两名患者为纯合子的C等位基因在位置-24的ABCC2基因（MRP2的rs717620），其已经与遗传易感性肾小管细胞内积聚的TDF相关的多态性。总之，在HBV的患者虽然TDF的整体风险相关的严重的肾毒性似乎是微不足道的，既肾小球和肾小管功能应该在患者暴露于TDF进行仔细的监测，特别是当其他肾危险因素，例如动脉高血压，先前的历史接触ADV或年龄较大，存在。主动减量TDF可以预防的严重肾脏并发症的发展。

披露：

毛罗·维加诺 - 咨询：罗氏公司;口语和教学：Gilead Sciences公司，BMS

小威Zaltron - 口语与教学：BMS，MSD

弗朗西斯卡斯泰利 - 格兰特/研究支持：安斯泰来，辉瑞，雅培;独立承包商：BMS，Boheringer Ingheleim，欢跃，先灵葆雅，罗氏制药，西安杨森Cilag公司，诺华公司

马西莫科伦坡 - 咨询委员会或审查小组：BRISTOL-MEY-ERS-SQUIBB，先灵葆雅，罗氏，基列BRISTOL - 迈耶斯 -  SQUIBB，先灵葆雅，罗氏，基列扬森Cilag公司，艾琪尔顿;格兰特/研究支持：百MEYERS-SQUIBB，ROCHE，基列BRISTOL-MEY-ERS-SQUIBB，ROCHE，GILEAD;口语和教学：葛兰素史克，百时MEYERS-SQUIBB，先灵葆雅，罗氏，诺华，基列VERTEX，葛兰素史克，百时MEYERS-SQUIBB，先灵葆雅，罗氏，诺华，基列顶点赛诺菲

彼得Lampertico - 咨询委员会或审查小组：德国拜耳，德国拜耳;说起和教学领域：百时美施贵宝，罗氏，葛兰素史克，诺华公司，Gilead公司，百时美施贵宝，罗氏，葛兰素史克，诺华，吉利德

下面的人都没有透露：亚历山德拉Brocchieri，Angiola Spinetti，詹保罗曼吉亚，弗洛里亚纳法切蒂，亚历山德罗Fugazza

中华北极星

译的很差劲，要连猜带蒙才能懂。