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

Daan B E van Wessel; Richard J Thompson; Emmanuel Gonzales; Irena Jankowska; Benjamin L Shneider; Etienne Sokal; Tassos Grammatikopoulos; Agustina Kadaristiana; Emmanuel Jacquemin; Anne Spraul; Patryk Lipiński; Piotr Czubkowski; Nathalie Rock; Mohammad Shagrani; Dieter Broering; Talal Algoufi; Nejat Mazhar; Emanuele Nicastro; Deirdre Kelly; Gabriella Nebbia; Henrik Arnell; Björn Fischler; Jan B F Hulscher; Daniele Serranti; Cigdem Arikan; Dominique Debray; Florence Lacaille; Cristina Goncalves; Loreto Hierro; Gema Muñoz Bartolo; Yael Mozer-Glassberg; Amer Azaz; Jernej Brecelj; Antal Dezsőfi; Pier Luigi Calvo; Dorothee Krebs-Schmitt; Steffen Hartleif; Wendy L van der Woerd; Jian-She Wang; Li-Ting Li; Özlem Durmaz; Nanda Kerkar; Marianne Hørby Jørgensen; Ryan Fischer; Carolina Jimenez-Rivera; Seema Alam; Mara Cananzi; Noémie Laverdure; Cristina Targa Ferreira; Felipe Ordonez; Heng Wang; Valerie Sency; Kyung Mo Kim; Huey-Ling Chen; Elisa Carvalho; Alexandre Fabre; Jesus Quintero Bernabeu; Estella M Alonso; Ronald J Sokol; Frederick J Suchy; Kathleen M Loomes; Patrick J McKiernan; Philip Rosenthal; Yumirle Turmelle; Girish S Rao; Simon Horslen; Binita M Kamath; Maria Rogalidou; Wikrom W Karnsakul; Bettina Hansen; Henkjan J Verkade; Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium

doi:10.1002/hep.31787

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

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

Daan B E van Wessel, Richard J Thompson, Emmanuel Gonzales, Irena Jankowska, Benjamin L Shneider, Etienne Sokal, Tassos Grammatikopoulos, Agustina Kadaristiana, Emmanuel Jacquemin, Anne Spraul, …

Hepatology (Baltimore, Md.), Vol.74(2), pp.892-906

08/2021

DOI: https://doi.org/10.1002/hep.31787

PMID: 33666275

Abstract

Adenosine Triphosphatases - deficiency

Adenosine Triphosphatases - genetics

Adolescent

Bile Acids and Salts - blood

Bile Ducts, Intrahepatic - surgery

Child

Child, Preschool

Cholestasis, Intrahepatic - blood

Cholestasis, Intrahepatic - genetics

Cholestasis, Intrahepatic - mortality

Cholestasis, Intrahepatic - surgery

Codon, Nonsense

Female

Follow-Up Studies

Humans

Infant

Liver Transplantation - statistics & numerical data

Male

Prognosis

Prospective Studies

Retrospective Studies

Risk Assessment - methods

Risk Assessment - statistics & numerical data

Survival Analysis

Treatment Outcome

Young Adult

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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Title: Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency
Creators - without role: Daan B E van Wessel - University Medical Center Groningen
Richard J Thompson - Institute of Liver StudiesKing's College HospitalLondonUnited Kingdom
Emmanuel Gonzales - Assistance Publique – Hôpitaux de Paris
Irena Jankowska - ERN GUARD-Heart
Benjamin L Shneider - Baylor College of Medicine
Etienne Sokal - Cliniques Universitaires Saint-Luc
Tassos Grammatikopoulos - King's College Hospital
Agustina Kadaristiana - King's College Hospital
Emmanuel Jacquemin - Inserm
Anne Spraul - University of Paris-Saclay
Patryk Lipiński - ERN GUARD-Heart
Piotr Czubkowski - ERN GUARD-Heart
Nathalie Rock - Cliniques Universitaires Saint-Luc
Mohammad Shagrani - King Faisal Specialist Hospital & Research Centre
Dieter Broering - King Faisal Specialist Hospital & Research Centre
Talal Algoufi - King Faisal Specialist Hospital & Research Centre
Nejat Mazhar - King Faisal Specialist Hospital & Research Centre
Emanuele Nicastro - Ospedale Papa Giovanni XXIII
Deirdre Kelly - ERN GUARD-Heart
Gabriella Nebbia - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Henrik Arnell - ERN GUARD-Heart
Björn Fischler - ERN GUARD-Heart
Jan B F Hulscher - ERN GUARD-Heart
Daniele Serranti - Meyer Children's Hospital
Cigdem Arikan - Koç University
Dominique Debray - 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
Florence Lacaille - 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
Cristina Goncalves - Coimbra University Hospital CenterCoimbraPortugal
Loreto Hierro - ERN GUARD-Heart
Gema Muñoz Bartolo - Pediatric Liver ServiceLa Paz University HospitalMadridSpain
Yael Mozer-Glassberg - Schneider Children's Medical Center
Amer Azaz - Shaikh Khalifa Medical City
Jernej Brecelj - Ljubljana University Medical Centre
Antal Dezsőfi - Semmelweis University
Pier Luigi Calvo - Pediatic Gastroenterology UnitRegina Margherita Children's HospitalAzienda Ospedaliera Città Della Salute e Della Scienza University HospitalTorinoItaly
Dorothee Krebs-Schmitt - Klinik und Poliklinik für Kinder- und Jugendmedizin
Steffen Hartleif - ERN GUARD-Heart
Wendy L van der Woerd - Wilhelmina Children's Hospital
Jian-She Wang - Children's Hospital of Fudan University
Li-Ting Li - Children's Hospital of Fudan UniversityShanghaiChina
Özlem Durmaz - Istanbul University
Nanda Kerkar - University of Rochester Medical Center
Marianne Hørby Jørgensen - Pediatric and Adolescent DepartmentDepartment of Pediatrics and Adolescent MedicineRigshospitalet Copenhagen University HospitalCopenhagenDenmark
Ryan Fischer - Children's Mercy Hospital
Carolina Jimenez-Rivera - Children's Hospital of Eastern Ontario
Seema Alam - Institute of Liver and Biliary Sciences
Mara Cananzi - ERN GUARD-Heart
Noémie Laverdure - ERN GUARD-Heart
Cristina Targa Ferreira - Pediatric GastroenterologyHospital da Criança Santo AntônioPorto AllegreBrazil
Felipe Ordonez - Institute of Cardiology
Heng Wang - Center For Children With Special Needs
Valerie Sency - Center For Children With Special Needs
Kyung Mo Kim - Department of PediatricsAsan Medical Center Children's HospitalSeoulSouth Korea
Huey-Ling Chen - National Taiwan University Hospital
Elisa Carvalho - Pediatric Gastroenterology and HepatologyBrasília Children's HospitalBrasiliaBrazil
Alexandre Fabre - Aix-Marseille University
Jesus Quintero Bernabeu - Pediatric Hepatology and Liver Transplant UnitBarcelonaSpain
Estella M Alonso - Research Network
Ronald J Sokol - Research Network
Frederick J Suchy - Research Network
Kathleen M Loomes - Research Network
Patrick J McKiernan - Research Network
Philip Rosenthal - Research Network
Yumirle Turmelle - Research Network
Girish S Rao - Riley Hospital for ChildrenIndiana University School of MedicineIndianapolisINUSA
Simon Horslen - Research Network
Binita M Kamath - SickKids Foundation
Maria Rogalidou - Iaso Children’s Hospital
Wikrom W Karnsakul - Johns Hopkins Medicine
Bettina Hansen - University Health Network
Henkjan J Verkade - ERN GUARD-Heart
Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium
Publication Details: Hepatology (Baltimore, Md.), Vol.74(2), pp.892-906
Grant note: U01 DK062453 / NIDDK NIH HHS U01 DK062431 / NIDDK NIH HHS U01 DK103149 / NIDDK NIH HHS U01 DK062500 / NIDDK NIH HHS UL1 TR002535 / NCATS NIH HHS U01 DK062466 / NIDDK NIH HHS UL1 TR000003 / NCATS NIH HHS UL1 TR001872 / NCATS NIH HHS U01 DK062481 / NIDDK NIH HHS U01 DK084536 / NIDDK NIH HHS
Identifiers: 9913670408331
Academic Unit: King Faisal University; Alfaisal University
Language: English
Resource Type: Journal article