Publication:
Impact of genotype, serum bile acids, and surgical biliary diversion on native liver survival in FIC1 deficiency

dc.contributor.coauthorvan Wessel, D. B. E.
dc.contributor.coauthorThompson, R. J.
dc.contributor.coauthorGonzales, E.
dc.contributor.coauthorJankowska, I.
dc.contributor.coauthorShneider, B. L.
dc.contributor.coauthorSokal, E.
dc.contributor.coauthorGrammatikopoulos, T.
dc.contributor.coauthorKadaristiana, A.
dc.contributor.coauthorJacquemin, E.
dc.contributor.coauthorSpraul, A.
dc.contributor.coauthorLipiński, P.
dc.contributor.coauthorCzubkowski, P.
dc.contributor.coauthorRock, N.
dc.contributor.coauthorShagrani, M.
dc.contributor.coauthorBroering, D.
dc.contributor.coauthorAlgoufi, T.
dc.contributor.coauthorMazhar, N.
dc.contributor.coauthorNicastro, E.
dc.contributor.coauthorKelly, D.
dc.contributor.coauthorNebbia, G.
dc.contributor.coauthorArnell, H.
dc.contributor.coauthorFischler, B.
dc.contributor.coauthorHulscher, J. B. F.
dc.contributor.coauthorSerranti, D.
dc.contributor.coauthorDebray, D.
dc.contributor.coauthorLacaille, F.
dc.contributor.coauthorGoncalves, C.
dc.contributor.coauthorHierro, L.
dc.contributor.coauthorMuñoz Bartolo, G.
dc.contributor.coauthorMozer-Glassberg, Y.
dc.contributor.coauthorAzaz, A.
dc.contributor.coauthorBrecelj, J.
dc.contributor.coauthorDezsőfi, A.
dc.contributor.coauthorLuigi Calvo, P.
dc.contributor.coauthorKrebs-Schmitt, D.
dc.contributor.coauthorHartleif, S.
dc.contributor.coauthorvan der Woerd, W. L.
dc.contributor.coauthorWang, J. S.
dc.contributor.coauthorLi, L. T.
dc.contributor.coauthorDurmaz, Ö.
dc.contributor.coauthorKerkar, N.
dc.contributor.coauthorHørby Jørgensen, M.
dc.contributor.coauthorFischer, R.
dc.contributor.coauthorJimenez-Rivera, C.
dc.contributor.coauthorAlam, S.
dc.contributor.coauthorCananzi, M.
dc.contributor.coauthorLaverdure, N.
dc.contributor.coauthorFerreira, C. T.
dc.contributor.coauthorOrdonez, F.
dc.contributor.coauthorWang, H.
dc.contributor.coauthorSency, V.
dc.contributor.coauthorKim, K. M.
dc.contributor.coauthorChen, H. L.
dc.contributor.coauthorCarvalho, E.
dc.contributor.coauthorFabre, A.
dc.contributor.coauthorQuintero Bernabeu, J.
dc.contributor.coauthorAlonso, E. M.
dc.contributor.coauthorSokol, R. J.
dc.contributor.coauthorSuchy, F. J.
dc.contributor.coauthorLoomes, K. M.
dc.contributor.coauthorMcKiernan, P. J.
dc.contributor.coauthorRosenthal, P.
dc.contributor.coauthorTurmelle, Y.
dc.contributor.coauthorRao, G. S.
dc.contributor.coauthorHorslen, S.
dc.contributor.coauthorKamath, B. M.
dc.contributor.coauthorRogalidou, M.
dc.contributor.coauthorKarnsakul, W. W.
dc.contributor.coauthorHansen, B.
dc.contributor.coauthorVerkade, H. J.
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorArıkan, Çiğdem
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T12:32:32Z
dc.date.issued2021
dc.description.abstractMutations in ATP8B1 can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1 (PFIC1). 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 novel insights by using the largest genetically defined cohort of FIC1 deficiency patients 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 PPTM), 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 18y. NLS was comparable between FIC1-A, FIC1-B, and FIC1-C (%NLS at age 10y: 67%, 41%, and 59%, respectively; P=0.12), despite FIC1-C undergoing SBD less often (%SBD at age 10y: 65%, 57%, and 45%, respectively; P=0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10y; sBAs <194 µmol/L: 49% versus 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 <65μmol/L (P=0.05) tended to be associated with improved NLS. Conclusion: Less than half of FIC1 deficiency patients 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.
dc.description.fulltextYES
dc.description.indexedbyPubMed
dc.description.issue2
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipUniversity of Colorado
dc.description.sponsorshipBaylor College of Medicine
dc.description.sponsorshipChildren’s Hospital of Philadelphia
dc.description.sponsorshipChildren’s Hospital of Pittsburgh
dc.description.sponsorshipSt Louis Children’s Hospital
dc.description.sponsorshipRiley Hospital for Children
dc.description.sponsorshipSeattle Children’s Hospital
dc.description.sponsorshipM.D./Ph.D. Scholarship from the University of Groningen
dc.description.sponsorshipEuropean Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Networking Grant 2019
dc.description.sponsorshipChilDReN National Institutes of Health Grants
dc.description.sponsorshipAnn & Robert H. Lurie Children’s Hospital
dc.description.sponsorshipAlbireo and Mirum Pharmaceuticals
dc.description.versionPublisher version
dc.description.volume74
dc.identifier.doi10.1002/hep.31787
dc.identifier.eissn1527-3350
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR02821
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85110180026
dc.identifier.urihttps://hdl.handle.net/20.500.14288/1979
dc.keywordsATP8B1
dc.keywordsFIC1 deficiency
dc.keywordsPFIC1
dc.keywordsSerum bile acids
dc.keywordsSurgical biliary diversion
dc.language.isoeng
dc.publisherWiley
dc.relation.grantnoU01DK62453
dc.relation.grantnoUL1 TR002535
dc.relation.grantnoU01DK103149
dc.relation.grantnoU01DK062481
dc.relation.grantnoUL1TR000003
dc.relation.grantnoU01DK062466
dc.relation.grantnoU01DK062500
dc.relation.grantnoUL1TR001872
dc.relation.grantnoU01DK084536
dc.relation.grantnoDK084575
dc.relation.ispartofHepatology
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/9473
dc.titleImpact of genotype, serum bile acids, and surgical biliary diversion on native liver survival in FIC1 deficiency
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorArıkan, Çiğdem
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2School of Medicine
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