title: The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration.
abstract: There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome.
  
  
  
  PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).
authors.affiliation: University of Utah, Salt Lake City, UT.
authors.forename: Mark R
authors.identifier: 0000-0003-0459-9404
authors.initials: MR
authors.lastname: Deneau
authors.affiliation: University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Wael
authors.initials: W
authors.lastname: El-Matary
authors.affiliation: Yale University School of Medicine, New Haven, CT.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Valentino
authors.affiliation: State University of New York Buffalo, Buffalo, NY.
authors.forename: Reham
authors.initials: R
authors.lastname: Abdou
authors.affiliation: Prince Salman North West Armed Forces Hospital, Tabuk, Saudi Arabia.
authors.forename: Khaled
authors.initials: K
authors.lastname: Alqoaer
authors.affiliation: University of California San Francisco, San Francisco, CA, and Texas Children's Hospital, Houston, TX.
authors.forename: Mansi
authors.initials: M
authors.lastname: Amin
authors.affiliation: The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Achiya Z
authors.initials: AZ
authors.lastname: Amir
authors.affiliation: Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Auth
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Fateh
authors.initials: F
authors.lastname: Bazerbachi
authors.affiliation: University College Dublin, Dublin, Ireland.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Broderick
authors.affiliation: University of Rochester Medical Center, Rochester, NY.
authors.forename: Albert
authors.initials: A
authors.lastname: Chan
authors.affiliation: University of Colorado School of Medicine, Aurora, CO.
authors.forename: Jillian
authors.initials: J
authors.lastname: Cotter
authors.affiliation: University of Utah, Salt Lake City, UT.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Doan
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Mounif
authors.initials: M
authors.lastname: El-Youssef
authors.affiliation: Sapienza University of Rome, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ferrari
authors.affiliation: Mayo Clinic, Rochester, MN.|Nemours Alfred I duPont Hospital For Children, Wilmington, DE.
authors.forename: Katryn N
authors.initials: KN
authors.lastname: Furuya
authors.affiliation: Lille University Hospital of Lille, Lille, France.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Gottrand
authors.affiliation: Lille University Hospital of Lille, Lille, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Gottrand
authors.affiliation: Emory University School of Medicine, Atlanta, GA.
authors.forename: Nitika
authors.initials: N
authors.lastname: Gupta
authors.affiliation: University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Homan
authors.affiliation: University of Toronto, Toronto, Ontario, Canada.
authors.forename: Binita M
authors.initials: BM
authors.lastname: Kamath
authors.affiliation: University of Ulsan, Seoul, South Korea.
authors.forename: Kyung Mo
authors.initials: KM
authors.lastname: Kim
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
authors.affiliation: University of Liverpool, Liverpool, and University of Manchester, Manchester, UK.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Konidari
authors.affiliation: Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Koot
authors.affiliation: University of Naples Federico II, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Iorio
authors.affiliation: Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Ledder
authors.affiliation: University of Colorado School of Medicine, Aurora, CO.
authors.forename: Cara
authors.initials: C
authors.lastname: Mack
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martinez
authors.affiliation: Texas Children's Hospital, Houston, TX, and Phoenix Children's Hospital, Phoenix, AZ.
authors.forename: Tamir
authors.initials: T
authors.lastname: Miloh
authors.affiliation: Children's National Medical Center, Washington, DC.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Mohan
authors.affiliation: University College Dublin, Dublin, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: O'Cathain
authors.affiliation: University of Athens, Athens, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Papadopoulou
authors.affiliation: University of Toronto, Toronto, Ontario, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ricciuto
authors.affiliation: University of Rochester Medical Center, Rochester, NY.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Saubermann
authors.affiliation: Memorial University, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Sathya
authors.affiliation: Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Shteyer
authors.affiliation: Palacky University, Olomouc, Czech Republic.
authors.forename: Vratislav
authors.initials: V
authors.lastname: Smolka
authors.affiliation: Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Atushi
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Northwest Pediatric Gastroenterology LLC, Portland, OR.
authors.forename: Raghu
authors.initials: R
authors.lastname: Varier
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Veena
authors.initials: V
authors.lastname: Venkat
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Vitola
authors.affiliation: Emory University School of Medicine, Atlanta, GA.
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Vos
authors.affiliation: Children's Health Memorial Institute, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Woynarowski
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Yap
authors.affiliation: University of Utah, Salt Lake City, UT.
authors.forename: M Kyle
authors.initials: MK
authors.lastname: Jensen
mesh_terms: D000704:Analysis of Variance; D001707:Biopsy, Needle; D002648:Child; D015209:Cholangitis, Sclerosing / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D038622:Internationality; D007564:Japan; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000379:methods* / Q000401:mortality; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis