title: Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis.
abstract: To evaluate the efficacy of nontransplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 with Alagille syndrome (ALGS), 16 with familial intrahepatic cholestasis-1 (FIC1), 18 with bile salt export pump (BSEP) disease, and 4 others with low γ-glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBDs), 11 ileal exclusions (IEs), and seven gallbladder-to-colon (GBC) diversions. Serum total bilirubin decreased after PEBD in FIC1 (8.1 ± 4.0 vs. 2.9 ± 4.1 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.02), but not in ALGS or BSEP. Total serum cholesterol decreased after PEBD in ALGS patients (695 ± 465 vs. 457 ± 319 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182 ± 70 vs. 260 ± 73 IU/L, preoperatively vs. 24 months; P = 0.03), but not in FIC1 or BSEP. ALGS, FIC1, and BSEP patients experienced less severely scored pruritus after PEBD (ALGS, 100% vs. 9% severe; FIC1, 64% vs. 10%; BSEP, 50% vs. 20%, preoperatively vs. >24 months postoperatively, respectively; P < 0.001). ALGS patients experienced a trend toward greater freedom from xanthomata after PEBD. There was a trend toward decreased pruritus in FIC1 after IE and GBC. Vitamin K supplementation increased in ALGS after PEBD (33% vs. 77%; P = 0.03). Overall, there were 15 major complications after surgery. Twelve patients (3 ALGS, 3 FIC1, and 6 BSEP) subsequently underwent liver transplantation.
  
  
  
  This was a multicenter analysis of nontransplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally, although not uniformly, result in improvement of pruritus and cholestasis. (Hepatology 2017;65:1645-1654).
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Kasper S
authors.initials: KS
authors.lastname: Wang
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Greg
authors.initials: G
authors.lastname: Tiao
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Bass
authors.affiliation: Texas Children's Hospital, Houston, TX.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Hertel
authors.affiliation: Children's Hospital at Johns Hopkins, Baltimore, MD.
authors.forename: Douglas
authors.initials: D
authors.lastname: Mogul
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Nanda
authors.initials: N
authors.lastname: Kerkar
authors.affiliation: Children's Healthcare of Atlanta, Atlanta, GA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Clifton
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Azen
authors.affiliation: University of California, San Francisco, CA.
authors.forename: Laura
authors.initials: L
authors.lastname: Bull
authors.affiliation: University of California, San Francisco, CA.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.affiliation: Children's Hospital at Johns Hopkins, Baltimore, MD.
authors.forename: Dylan
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Superina
authors.affiliation: Mount Sinai Medical Center, New York, NY.
authors.forename: Ronen
authors.initials: R
authors.lastname: Arnon
authors.affiliation: Riley Hospital for Children, Indianapolis, IN.
authors.forename: Molly
authors.initials: M
authors.lastname: Bozic
authors.affiliation: Texas Children's Hospital, Houston, TX.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Brandt
authors.affiliation: St. Louis Children's Hospital, St. Louis, MO.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dillon
authors.affiliation: The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Fecteau
authors.affiliation: Mount Sinai Medical Center, New York, NY.
authors.forename: Kishore
authors.initials: K
authors.lastname: Iyer
authors.affiliation: The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Binita
authors.initials: B
authors.lastname: Kamath
authors.affiliation: Children's Healthcare of Atlanta, Atlanta, GA.
authors.forename: Saul
authors.initials: S
authors.lastname: Karpen
authors.affiliation: Children's Hospital Colorado, Aurora, CO.
authors.forename: Frederick
authors.initials: F
authors.lastname: Karrer
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Loomes
authors.affiliation: Children's Hospital Colorado, Aurora, CO.
authors.forename: Cara
authors.initials: C
authors.lastname: Mack
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Peter
authors.initials: P
authors.lastname: Mattei
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Alexander
authors.initials: A
authors.lastname: Miethke
authors.affiliation: Children's Hospital of Pittsburgh, Pittsburgh, PA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Soltys
authors.affiliation: St. Louis Children's Hospital, St. Louis, MO.
authors.forename: Yumirle P
authors.initials: YP
authors.lastname: Turmelle
authors.affiliation: Riley Hospital for Children, Indianapolis, IN.
authors.forename: Karen
authors.initials: K
authors.lastname: West
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zagory
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Cat
authors.initials: C
authors.lastname: Goodhue
authors.affiliation: Texas Children's Hospital, Houston, TX.|Children's Hospital of Pittsburgh, Pittsburgh, PA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Shneider
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000601:surgery*; D013505:Digestive System Surgical Procedures / Q000009:adverse effects / Q000706:statistics & numerical data*; D004764:Enterohepatic Circulation; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome