Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

Autor:	van Wessel DBE; Pediatric Gastroenterology and HepatologyUniversity Medical Center GroningenUniversity of GroningenGroningenthe Netherlands., Thompson RJ; Institute of Liver StudiesKing's College HospitalLondonUnited Kingdom., Gonzales E; Pediatric Hepatology & Pediatric Liver Transplant DepartmentCentre de Référence de l'Atrésie des Voies Biliaires et des Cholestases GénétiquesFilière de Santé des Maladies Rares du Foie de l'enfant et de l'adulteEuropean Reference Network RARE-LIVERAssistance Publique-Hôpitaux de ParisFaculté de Médecine Paris-SaclayCHU BicêtreParisFrance.; European Reference Network on Hepatological Diseases., Jankowska I; European Reference Network on Hepatological Diseases.; Gastroenterology, Hepatology, Nutritional Disorders and Pediatricsthe Children's Memorial Health InstituteWarsawPoland., Shneider BL; Division of Pediatric Gastroenterology, Hepatology, and NutritionDepartment of PediatricsBaylor College of MedicineHoustonTXUSA.; Childhood Liver Disease Research Network (ChiLDReN)., Sokal E; European Reference Network on Hepatological Diseases.; Cliniques St. LucUniversité Catholique de LouvainBrusselsBelgium., Grammatikopoulos T; Institute of Liver StudiesKing's College HospitalLondonUnited Kingdom., Kadaristiana A; Institute of Liver StudiesKing's College HospitalLondonUnited Kingdom., Jacquemin E; Pediatric Hepatology & Pediatric Liver Transplant DepartmentCentre de Référence de l'Atrésie des Voies Biliaires et des Cholestases GénétiquesFilière de Santé des Maladies Rares du Foie de l'enfant et de l'adulteEuropean Reference Network RARE-LIVERAssistance Publique-Hôpitaux de ParisFaculté de Médecine Paris-SaclayCHU BicêtreParisFrance.; INSERMUMR-S 1193Université Paris-SaclayOrsayFrance., Spraul A; INSERMUMR-S 1193Université Paris-SaclayOrsayFrance.; Biochemistry UnitCentre de Référence de l'Atrésie des Voies Biliaires et des Cholestases GénétiquesFilière de Santé des Maladies Rares du Foie de l'enfant et de l'adulteEuropean Reference Network RARE-LIVERAssistance Publique-Hôpitaux de ParisFaculté de Médecine Paris-SaclayCHU BicêtreParisFrance., Lipiński P; European Reference Network on Hepatological Diseases.; Gastroenterology, Hepatology, Nutritional Disorders and Pediatricsthe Children's Memorial Health InstituteWarsawPoland., Czubkowski P; European Reference Network on Hepatological Diseases.; Gastroenterology, Hepatology, Nutritional Disorders and Pediatricsthe Children's Memorial Health InstituteWarsawPoland., Rock N; Cliniques St. LucUniversité Catholique de LouvainBrusselsBelgium., Shagrani M; Department of Liver & SB Transplant & Hepatobiliary-Pancreatic SurgeryKing Faisal Specialist Hospital & Research CenterRiyadhSaudi Arabia.; College of MedicineAlfaisal UniversityRiyadhSaudi Arabia., Broering D; Department of Liver & SB Transplant & Hepatobiliary-Pancreatic SurgeryKing Faisal Specialist Hospital & Research CenterRiyadhSaudi Arabia., Algoufi T; Department of Liver & SB Transplant & Hepatobiliary-Pancreatic SurgeryKing Faisal Specialist Hospital & Research CenterRiyadhSaudi Arabia., Mazhar N; Department of Liver & SB Transplant & Hepatobiliary-Pancreatic SurgeryKing Faisal Specialist Hospital & Research CenterRiyadhSaudi Arabia., Nicastro E; Pediatric Hepatology, Gastroenterology and TransplantationOspedale Papa Giovanni XXIIIBergamoItaly., Kelly D; European Reference Network on Hepatological Diseases.; Liver UnitBirmingham Women's and Children's HospitalUniversity of BirminghamBirminghamUnited Kingdom., Nebbia G; Servizio Di Epatologia e Nutrizione PediatricaFondazione Irccs Ca' Granda Ospedale Maggiore PoliclinicoMilanoItaly., Arnell H; European Reference Network on Hepatological Diseases.; Pediatric Digestive DiseasesAstrid Lindgren Children's HospitalCLINTECKarolinska InstitutetKarolinska University HospitalStockholmSweden., Fischler B; European Reference Network on Hepatological Diseases.; Pediatric Digestive DiseasesAstrid Lindgren Children's HospitalCLINTECKarolinska InstitutetKarolinska University HospitalStockholmSweden., Hulscher JBF; European Reference Network on Hepatological Diseases.; Pediatric SurgeryUniversity Medical Center GroningenGroningenthe Netherlands., Serranti D; Pediatric and Liver UnitMeyer Children's University Hospital of FlorenceFlorenceItaly., Arikan C; Pediatric GI and Hepatology Liver Transplantation CenterKuttam System in Liver MedicineKoc University School of MedicineIstanbulTurkey., Debray D; Pediatric Hepatology unit, Reference Center for Biliary Atresia and Genetic Cholestatic DiseasesFilière de Santé des Maladies Rares du Foie de l'enfant et de l'adulteEuropean Reference Network RARE-LIVERAPHP-Neckler Enfants Malades University HospitalFaculté de Médecine Paris-CentreParisFrance., Lacaille F; Pediatric Hepatology unit, Reference Center for Biliary Atresia and Genetic Cholestatic DiseasesFilière de Santé des Maladies Rares du Foie de l'enfant et de l'adulteEuropean Reference Network RARE-LIVERAPHP-Neckler Enfants Malades University HospitalFaculté de Médecine Paris-CentreParisFrance., Goncalves C; European Reference Network on Hepatological Diseases.; Coimbra University Hospital CenterCoimbraPortugal., Hierro L; European Reference Network on Hepatological Diseases.; Pediatric Liver ServiceLa Paz University HospitalMadridSpain., Muñoz Bartolo G; European Reference Network on Hepatological Diseases.; Pediatric Liver ServiceLa Paz University HospitalMadridSpain., Mozer-Glassberg Y; Institute of Gastroenterology, Nutrition and Liver DiseasesSchneider Children's Medical Center of IsraelPetach TikvahIsrael., Azaz A; Sheikh Khalifa Medical CityAbu DhabiUnited Arab Emirates., Brecelj J; Department of Gastroenterology, Hepatology and NutritionUniversity Children's Hospital LjubljanaLjubljanaSlovenia.; Department of PediatricsFaculty of MedicineUniversity of LjubljanaLjubljanaSlovenia., Dezsőfi A; First Department of PediatricsSemmelweis UniversityBudapestHungary., Luigi Calvo P; Pediatic Gastroenterology UnitRegina Margherita Children's HospitalAzienda Ospedaliera Città Della Salute e Della Scienza University HospitalTorinoItaly., Krebs-Schmitt D; Klinik Für Kinder-Und JugendmedizinUniversitätsklinikum Hamburg EppendorfHamburgGermany., Hartleif S; European Reference Network on Hepatological Diseases.; University Children's Hospital TϋbingenTϋbingenGermany., van der Woerd WL; Pediatric Gastroenterology, Hepatology and NutritionWilhelmina Children's HospitalUniversity Medical Center UtrechtUtrechtthe Netherlands., Wang JS; Children's Hospital of Fudan UniversityShanghaiChina., Li LT; Children's Hospital of Fudan UniversityShanghaiChina., Durmaz Ö; Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey., Kerkar N; Pediatric Gastroenterology, Hepatology and NutritionUniversity of Rochester Medical CenterRochesterNYUSA., Hørby Jørgensen M; European Reference Network on Hepatological Diseases.; Pediatric and Adolescent DepartmentDepartment of Pediatrics and Adolescent MedicineRigshospitalet Copenhagen University HospitalCopenhagenDenmark., Fischer R; Section of Hepatology and Transplant MedicineChildren's Mercy HospitalKansas CityMOUSA., Jimenez-Rivera C; Department of PediatricsChildren's Hospital of Eastern OntarioUniversity of OttawaOttawaCanada., Alam S; Pediatric HepatologyInstitute of Liver and Biliary SciencesNew DelhiIndia., Cananzi M; European Reference Network on Hepatological Diseases.; Pediatric Gastroenterology and HepatologyUniversity Hospital of PadovaPadovaItaly., Laverdure N; European Reference Network on Hepatological Diseases.; Service de Gastroentérologie, Hépatologie et Nutrition PédiatriquesHospices Civils de LyonHôpital Femme Mère EnfantLyonFrance., Targa Ferreira C; Pediatric GastroenterologyHospital da Criança Santo AntônioPorto AllegreBrazil., Ordonez F; Fundación Cardioinfantil Instituto de CardiologiaPediatric Gastroenterology and HepatologyBogotáColombia., Wang H; DDC Clinic Center for Special Needs ChildrenMiddlefieldOHUSA., Sency V; DDC Clinic Center for Special Needs ChildrenMiddlefieldOHUSA., Mo Kim K; Department of PediatricsAsan Medical Center Children's HospitalSeoulSouth Korea., Chen HL; Division of Pediatric Gastroenterology, Hepatology and NutritionNational Taiwan University Children's HospitalTaipeiTaiwan., Carvalho E; Pediatric Gastroenterology and HepatologyBrasília Children's HospitalBrasiliaBrazil., Fabre A; INSERMMMGAix Marseille UniversityMarseilleFrance.; Serveice de Pédiatrie MultidisciplinaireTimone EnfantMarseilleFrance., Quintero Bernabeu J; European Reference Network on Hepatological Diseases.; Pediatric Hepatology and Liver Transplant UnitBarcelonaSpain., Alonso EM; Childhood Liver Disease Research Network (ChiLDReN).; Division of Pediatric Gastroenterology, Hepatology and NutritionAnn & Robert H. Lurie Children's HospitalChicagoILUSA., Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN).; Section of Pediatric Gastroenterology, Hepatology and NutritionDepartment of PediatricsChildren's Hospital ColoradoUniversity of Colorado School of MedicineAuroraCOUSA., Suchy FJ; Childhood Liver Disease Research Network (ChiLDReN).; Icahn School of Medicine at Mount SinaiMount Sinai Kravis Children's HospitalNew YorkNYUSA., Loomes KM; Childhood Liver Disease Research Network (ChiLDReN).; Division of Gastroenterology, Hepatology and NutritionChildren's Hospital of PhiladelphiaPhiladelphiaPAUSA., McKiernan PJ; Childhood Liver Disease Research Network (ChiLDReN).; Department of Pediatric Gastroenterology and HepatologyUniversity of Pittsburgh Medical Center Children's Hospital of PittsburghPittsburghPAUSA., Rosenthal P; Childhood Liver Disease Research Network (ChiLDReN).; Department of Pediatrics and SurgeryUCSF Benioff Children's HospitalUniversity of California San Francisco School of MedicineSan FranciscoCAUSA., Turmelle Y; Childhood Liver Disease Research Network (ChiLDReN).; Section of HepatologyDepartment of PediatricsSt. Louis Children's HospitalWashington University School of MedicineSt. LouisMOUSA., Rao GS; Childhood Liver Disease Research Network (ChiLDReN).; Riley Hospital for ChildrenIndiana University School of MedicineIndianapolisINUSA., Horslen S; Childhood Liver Disease Research Network (ChiLDReN).; Department of PediatricsSeattle Children's HospitalUniversity of WashingtonSeattleWAUSA., Kamath BM; Childhood Liver Disease Research Network (ChiLDReN).; The Hospital for Sick ChildrenUniversity of TorontoTorontoCanada., Rogalidou M; Division of Pediatric Gastroenterology & HepatologyFirst Pediatrics DepartmentUniversity of AthensAgia Sofia Children's HospitalAthensGreece., Karnsakul WW; Division of Pediatric Gastroenterology, Nutrition, and HepatologyDepartment of PediatricsJohns Hopkins University School of MedicineBaltimoreMDUSA., Hansen B; Toronto Center for Liver DiseaseUniversity Health NetworkTorontoCanada.; IHPMEUniversity of TorontoTorontoCanada., Verkade HJ; Pediatric Gastroenterology and HepatologyUniversity Medical Center GroningenUniversity of GroningenGroningenthe Netherlands.; European Reference Network on Hepatological Diseases.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2021 Aug; Vol. 74 (2), pp. 892-906. Date of Electronic Publication: 2021 Jul 13.
DOI:	10.1002/hep.31787
Abstrakt:	Background and Aims: 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. Approach and Results: 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. Conclusions: 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. (© The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
Databáze:	MEDLINE
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