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

被引：37

作者：

van Wessel, Daan B. E. ^{[1
]}

Thompson, Richard J. ^{[2
]}

Gonzales, Emmanuel ^{[3
,4
]}

Jankowska, Irena ^{[4
,5
]}

Shneider, Benjamin L. ^{[6
,7
]}

Sokal, Etienne ^{[4
,8
]}

Grammatikopoulos, Tassos ^{[2
]}

Kadaristiana, Agustina ^{[2
]}

Jacquemin, Emmanuel ^{[3
,9
]}

Spraul, Anne ^{[9
,10
]}

Lipinski, Patryk ^{[4
,5
]}

Czubkowski, Piotr ^{[4
,5
]}

Rock, Nathalie ^{[8
]}

Shagrani, Mohammad ^{[11
,12
]}

Broering, Dieter ^{[11
]}

Algoufi, Talal ^{[11
]}

Mazhar, Nejat ^{[11
]}

Nicastro, Emanuele ^{[13
]}

Kelly, Deirdre ^{[4
,14
]}

Nebbia, Gabriella ^{[15
]}

Arnell, Henrik ^{[4
,16
]}

Fischler, Bjorn ^{[4
,16
]}

Hulscher, Jan B. F. ^{[4
,17
]}

Serranti, Daniele ^{[18
]}

Arikan, Cigdem ^{[19
]}

Debray, Dominique ^{[20
]}

Lacaille, Florence ^{[20
]}

Goncalves, Cristina ^{[4
,21
]}

Hierro, Loreto ^{[4
,22
]}

Bartolo, Gema Munoz ^{[4
,22
]}

Mozer-Glassberg, Yael ^{[23
]}

Azaz, Amer ^{[24
]}

Brecelj, Jernej ^{[25
,26
]}

Dezsofi, Antal ^{[27
]}

Calvo, Pier Luigi ^{[28
]}

Krebs-Schmitt, Dorothee ^{[29
]}

Hartleif, Steffen ^{[4
,30
]}

van der Woerd, Wendy L. ^{[31
]}

Wang, Jian-She ^{[32
]}

Li, Li-Ting ^{[32
]}

Durmaz, Ozlem ^{[33
]}

Kerkar, Nanda ^{[34
]}

Jorgensen, Marianne Horby ^{[4
,35
]}

Fischer, Ryan ^{[36
]}

Jimenez-Rivera, Carolina ^{[37
]}

Alam, Seema ^{[38
]}

Cananzi, Mara ^{[4
,39
]}

Laverdure, Noemie ^{[4
,40
]}

Ferreira, Cristina Targa ^{[41
]}

Ordonez, Felipe ^{[42
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Pediat Gastroenterol & Hepatol, Groningen, Netherlands

[2] Kings Coll Hosp London, Inst Liver Studies, London, England

[3] CHU Bicetre, AP HP,European Reference Network RARE LIVER, Pediat Hepatol & Pediat Liver Transplant Dept,Fil, Fac Med Paris Saclay,Ctr Reference Atresie Voies, Paris, France

[4] European Reference Network Hepatol Dis, Warsaw, Poland

[5] Childrens Mem Hlth Inst, Gastroenterol Hepatol Nutr Disorders & Pediat, Warsaw, Poland

[6] Baylor Coll Med, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA

[7] Childhood Liver Dis Res Network ChiLDReN, Brussels, Belgium

[8] Catholic Univ Louvain, Clin St Luc, Brussels, Belgium

[9] Univ Paris Saclay, INSERM, UMR S 1193, Orsay, France

[10] CHU Bicetre, AP HP,European Reference Network RARE Liver, Biochem Unit,Filiere Sante Malad Rares Foie Enfan, Fac Med Paris Saclay,Ctr Reference Atresie Voies, Paris, France

[11] King Faisal Specialist Hosp & Res Ctr, Dept Liver & SB Transplant & Hepatobiliary Pancre, Riyadh, Saudi Arabia

[12] Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia

[13] Osped Papa Giovanni XXIII, Pediat Hepatol Gastroenterol & Transplantat, Bergamo, Italy

[14] Univ Birmingham, Birmingham Womens & Childrens Hosp, Liver Unit, Birmingham, W Midlands, England

[15] Fdn Irccs Ca Granda Osped Maggiore Policlin, Serv Epatol & Nutr Pediat, Milan, Italy

[16] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Karolinska Inst, CLINTEC,Pediat Digest Dis, Stockholm, Sweden

[17] Univ Med Ctr Groningen, Pediat Surg, Groningen, Netherlands

[18] Meyer Childrens Univ Hosp Florence, Pediat & Liver Unit, Florence, Italy

[19] Koc Univ, Pediat GI & Hepatol Liver Transplantat Ctr, Kuttam Syst Liver Med, Sch Med, Istanbul, Turkey

[20] Neckler Enfants Malad Univ Hosp, AP HP,European Reference Network RARE Liver, Reference Ctr Biliary Atresia & Genet Cholestat D, Pediat Hepatol Unit,Fac Med Paris Ctr,Filiere San, Paris, France

[21] Coimbra Univ Hosp Ctr, Coimbra, Portugal

[22] La Paz Univ Hosp, Pediat Liver Serv, Madrid, Spain

[23] Schneider Childrens Med Ctr Israel, Inst Gastroenterol Nutr & Liver Dis, Petah Tiqwa, Israel

[24] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates

[25] Univ Childrens Hosp Ljubljana, Dept Gastroenterol Hepatol & Nutr, Ljubljana, Slovenia

[26] Univ Ljubljana, Fac Med, Dept Pediat, Ljubljana, Slovenia

[27] Semmelweis Univ, Dept Pediat 1, Budapest, Hungary

[28] Azienda Osped Citta Salute & Sci Univ Hosp, Regina Margherita Childrens Hosp, Pediat Gastroenterol Unit, Turin, Italy

[29] Univ Klinikum Hamburg Eppendorf, Klin Kinder & Jugendmed, Hamburg, Germany

[30] Univ Childrens Hosp Tubingen, Tubingen, Germany

[31] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Pediat Gastroenterol Hepatol & Nutr, Utrecht, Netherlands

[32] Fudan Univ, Childrens Hosp, Shanghai, Peoples R China

[33] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey

[34] Univ Rochester, Med Ctr, Pediat Gastroenterol Hepatol & Nutr, Rochester, NY 14642 USA

[35] Copenhagen Univ Hosp, Pediat & Adolescent Dept, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark

[36] Childrens Mercy Hosp, Sect Hepatol & Transplant Med, Kansas City, MO 64108 USA

[37] Univ Ottawa, Childrens Hosp Eastern Ontario, Dept Pediat, Ottawa, ON, Canada

[38] Inst Liver & Biliary Sci, Pediat Hepatol, New Delhi, India

[39] Univ Hosp Padova, Pediat Gastroenterol & Hepatol, Padua, Italy

[40] Hop Femme Mere Enfant, Serv Gastroenterol Hepatol & Nutr Pediat, Hosp Civils Lyon, Lyon, France

[41] Hosp Crianca Santo Antonio, Pediat Gastroenterol, Porto Alegre, Brazil

[42] Fdn Cardioinfantil Inst Cardiol Pediat Gastroente, Bogota, Colombia

[43] DDC Clin Ctr Special Needs Children, Middlefield, OH USA

[44] Childrens Hosp, Dept Pediat, Asan Med Ctr, Seoul, South Korea

[45] Natl Taiwan Univ, Div Pediat Gastroenterol Hepatol & Nutr, Childrens Hosp, Taipei, Taiwan

[46] Brasilia Childrens Hosp, Pediat Gastroenterol & Hepatol, Brasilia, DF, Brazil

[47] Aix Marseille Univ, MMG, INSERM, Marseille, France

[48] La Timone, Enfant, Serveice Pediat Multidisciplinaire, Marseille, France

[49] Pediat Hepatol & Liver Transplant Unit, Barcelona, Spain

[50] Ann & Robert H Lurie Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Chicago, IL USA

来源：

HEPATOLOGY | 2021年 / 74卷 / 02期

关键词：

FAMILIAL INTRAHEPATIC CHOLESTASIS; SALT EXPORT PUMP; ABCB11; MUTATIONS; ATP8B1; GENE; TYPE-1; PFIC1; EXPRESSION; CHILDREN; DISEASE;

D O I：

10.1002/hep.31787

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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 mu mol/L: 49% vs. sBAs >= 194 mu mol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] mu mol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 mu mol/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.

引用

页码：892 / 906

页数：15

共 42 条

[1]

P4-ATPases as Phospholipid Flippases-Structure, Function, and Enigmas [J].

Andersen, Jens P. ;

Vestergaard, Anna L. ;

Mikkelsen, Stine A. ;

Mogensen, Louise S. ;

Chalat, Madhavan ;

Molday, Robert S. .

FRONTIERS IN PHYSIOLOGY, 2016, 7

[2]

Preoperative observations and short-term outcome after partial external biliary diversion in 13 patients with progressive familial intrahepatic cholestasis [J].

Arnell, Henrik ;

Bergdahl, Sven ;

Papadogiannakis, Nikos ;

Nemeth, Antal ;

Fischler, Bjoern .

JOURNAL OF PEDIATRIC SURGERY, 2008, 43 (07) :1312-1320

[3]

Liver transplantation for progressive familial intrahepatic cholestasis: Clinical and histopathological findings, outcome and impact on growth [J].

Aydogdu, Sema ;

Cakir, Murat ;

Arikan, C. ;

Turrigor, Gokhan ;

Yukesekkaya, Hasan Ali ;

YilrnaZ, Funda ;

Kilic, Murat .

PEDIATRIC TRANSPLANTATION, 2007, 11 (06) :634-640

[4]

Byler-like familial cholestasis in an extended kindred [J].

Bourke, B ;

Goggin, N ;

Walsh, D ;

Kennedy, S ;

Setchell, KDR ;

Drumm, B .

ARCHIVES OF DISEASE IN CHILDHOOD, 1996, 75 (03) :223-227

[5]

Progressive Familial Intrahepatic Cholestasis [J].

Bull, Laura N. ;

Thompson, Richard J. .

CLINICS IN LIVER DISEASE, 2018, 22 (04) :657-+

[6]

Outcomes of Surgical Management of Familial Intrahepatic Cholestasis 1 and Bile Salt Export Protein Deficiencies [J].

Bull, Laura N. ;

Pawlikowska, Ludmila ;

Strautnieks, Sandra ;

Jankowska, Irena ;

Czubkowski, Piotr ;

Dodge, Jennifer L. ;

Emerick, Karan ;

Wanty, Catherine ;

Wali, Sami ;

Blanchard, Samra ;

Lacaille, Florence ;

Byrne, Jane A. ;

van Eerde, Albertien M. ;

Kolho, Kaija-Leena ;

Houwen, Roderick ;

Lobritto, Steven ;

Hupertz, Vera ;

McClean, Patricia ;

Mieli-Vergani, Giorgina ;

Sokal, Etienne ;

Rosenthal, Philip ;

Whitington, Peter F. ;

Pawlowska, Joanna ;

Thompson, Richard J. .

HEPATOLOGY COMMUNICATIONS, 2018, 2 (05) :515-528

[7]

Fine-resolution mapping by haplotype evaluation:: the examples of PFIC1 and BRIC [J].

Bull, LN ;

Juijn, JA ;

Liao, M ;

van Eijk, MJT ;

Sinke, RJ ;

Stricker, NL ;

DeYoung, JA ;

Carlton, VEH ;

Baharloo, S ;

Klomp, LWJ ;

Abukawa, D ;

Barton, DE ;

Bass, NM ;

Bourke, B ;

Drumm, B ;

Jankowska, I ;

Lovisetto, P ;

McQuaid, S ;

Pawlowska, J ;

Tazawa, Y ;

Villa, E ;

Tygstrup, N ;

Berger, R ;

Knisely, AS ;

Houwen, RHJ ;

Freimer, NB .

HUMAN GENETICS, 1999, 104 (03) :241-248

[8]

A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis [J].

Bull, LN ;

van Eijk, MJT ;

Pawlikowska, L ;

DeYoung, JA ;

Juijn, JA ;

Liao, M ;

Klomp, LWJ ;

Lomri, N ;

Berger, R ;

Scharschmidt, BF ;

Knisely, AS ;

Houwen, RHJ ;

Freimer, NB .

NATURE GENETICS, 1998, 18 (03) :219-224

[9]

ATP8B1 Deficiency Disrupts the Bile Canalicular Membrane Bilayer Structure in Hepatocytes, But FXR Expression and Activity Are Maintained [J].

Cai, Shi-Ying ;

Gautam, Samir ;

Nguyen, Trong ;

Soroka, Carol J. ;

Rahner, Christoph ;

Boyer, James L. .

GASTROENTEROLOGY, 2009, 136 (03) :1060-1069

[10]

Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity [J].

Chen, F ;

Ananthanarayanan, M ;

Emre, S ;

Neimark, E ;

Bull, LN ;

Knisely, AS ;

Strautnieks, SS ;

Thompson, RJ ;

Magid, MS ;

Gordon, R ;

Balasubramanian, N ;

Suchy, FJ ;

Shneider, BL .

GASTROENTEROLOGY, 2004, 126 (03) :756-764

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