Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.
Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.
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DOI：
10.1002/hep.31787
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发表时间：
2021-08
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影响因子：
--
通讯作者：
Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium
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文献类型：
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作者：
van Wessel DBE;Thompson RJ;Gonzales E;Jankowska I;Shneider BL;Sokal E;Grammatikopoulos T;Kadaristiana A;Jacquemin E;Spraul A;Lipiński P;Czubkowski P;Rock N;Shagrani M;Broering D;Algoufi T;Mazhar N;Nicastro E;Kelly D;Nebbia G;Arnell H;Fischler B;Hulscher JBF;Serranti D;Arikan C;Debray D;Lacaille F;Goncalves C;Hierro L;Muñoz Bartolo G;Mozer-Glassberg Y;Azaz A;Brecelj J;Dezsőfi A;Luigi Calvo P;Krebs-Schmitt D;Hartleif S;van der Woerd WL;Wang JS;Li LT;Durmaz Ö;Kerkar N;Hørby Jørgensen M;Fischer R;Jimenez-Rivera C;Alam S;Cananzi M;Laverdure N;Targa Ferreira C;Ordonez F;Wang H;Sency V;Mo Kim K;Chen HL;Carvalho E;Fabre A;Quintero Bernabeu J;Alonso EM;Sokol RJ;Suchy FJ;Loomes KM;McKiernan PJ;Rosenthal P;Turmelle Y;Rao GS;Horslen S;Kamath BM;Rogalidou M;Karnsakul WW;Hansen B;Verkade HJ;Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium
ATP酶磷脂转运蛋白8B 1（ATP 8B 1）的突变可导致家族性肝内胆汁淤积1型（FIC 1）缺乏症或进行性家族性肝内胆汁淤积1型。FIC 1缺乏的罕见性在很大程度上阻碍了对其自然史、预测的蛋白质截短突变（PPTM）的影响以及血清胆汁酸（sBA）浓度和外科胆管分流术（SBD）与长期结局的可能相关性的详细分析。我们的目的是通过使用迄今为止最大的FIC 1缺陷症患者遗传定义队列来提供见解。这项多中心、回顾性和前瞻性相结合的研究纳入了130例复合杂合或纯合预测致病性ATP 8B 1变异的患者。根据PPTM的数量对患者进行分类（即，剪接位点，由于缺失或插入、无义、重复引起移码）、FIC 1-A（n = 67;无PPTM）、FIC 1-B（n = 29;一个PPTM）或FIC 1-C（n = 34;两个PPTM）。生存分析显示，18岁时的总体天然肝生存率（NLS）为44%。FIC 1-A、FIC 1-B和FIC 1-C之间的NLS相当（10岁时的% NLS分别为67%、41%和59%; P = 0.12），尽管FIC 1-C接受SBD的频率较低（10岁时的% SBD分别为65%、57%和45%; P = 0.03）。就诊时sBA与NLS呈负相关（10岁时NLS，sBA < 194 µmol/L：49% vs. sBA ≥ 194 µmol/L：15%; P = 0.03）。SBD降低sBA（230 [125 - 282]至74 [11 - 177] μmol/L; P = 0.005）。SBD（HR 0.55，95% CI 0.28 - 1.03，P = 0.06）和SBD后sBA浓度< 65 μmol/L（P = 0.05）往往与NLS改善相关。不到一半的FIC 1缺乏症患者成年后具有天然肝脏。PPTM的数量与FIC 1缺陷的自然史或预后无关。初始表现时和SBD后的sBA浓度提供的长期NLS预后信息有限。
Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long‐term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1‐A (n = 67; no PPTMs), FIC1‐B (n = 29; one PPTM), or FIC1‐C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1‐A, FIC1‐B, and FIC1‐C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1‐C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125‐282] to 74 [11‐177] μmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28‐1.03, P = 0.06) and post‐SBD sBA concentrations < 65 μmol/L (P = 0.05) tended to be associated with improved NLS. Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long‐term NLS.
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影响因子：
4.6
作者：
Miyagawa-Hayashino, Aya;Egawa, Hiroto;Uemoto, Shinji
通讯作者：
Uemoto, Shinji
DOI：
10.1001/archpedi.1969.02100030114014
发表时间：
1969-01-01
影响因子：
--
作者：
CLAYTON, RJ;IBER, FL;MCKUSICK, VA
通讯作者：
MCKUSICK, VA
影响因子：
2.4
作者：
Hollands, CM;Rivera-Pedrogo, FJ;Burnweit, CA
通讯作者：
Burnweit, CA
影响因子：
13.5
作者：
Folmer, Dineke E.;van der Mark, Vincent A.;Paulusma, Coen C.
通讯作者：
Paulusma, Coen C.
影响因子：
1.3
作者：
Aydogdu, Sema;Cakir, Murat;Kilic, Murat
通讯作者：
Kilic, Murat