title: Effect of Kasai procedure on hepatic outcome in Alagille syndrome.
abstract: OBJECTIVE
  Alagille syndrome (AGS) frequently presents with neonatal jaundice and can mimic other causes of high gamma-glutamyl transpeptidase (GGT) cholestasis, most notably biliary atresia. As a result infants with AGS may undergo intraoperative cholangiogram and even Kasai procedure. The aim of the study was to assess the hepatic outcomes of children with AGS who underwent the Kasai procedure.
  
  
  METHODS
  A retrospective review of the AGS clinical database at the Children's Hospital of Philadelphia was performed to identify clinically defined patients with AGS who underwent a Kasai. A cohort of Alagille control subjects was selected with equivalent symptoms of neonatal jaundice and matched for age and presence of cardiac anomaly. JAGGED1-mutation analysis was performed on available samples. Clinical courses were reviewed. Fisher exact and t tests were used for analysis.
  
  
  RESULTS
  Of the 430 patients with AGS, 19 underwent a Kasai procedure (K). The control cohort (C) consisted of 36 patients. Total bilirubin measured between 6 and 10 weeks of age in each cohort was equivalent (K: 9.6 mg/dL, C: 8.7 mg/dL); GGT levels were higher in the control group (K:493.4 U/L, C:574.4 U/L). Of note, the Kasai cohort had a significantly larger number of liver transplants (K: 9 [47.3%], C: 5 [13.9%], P = 0.01) and sustained higher mortality (K: 6 [31.6%], C: 1 [2.8%], P = 0.005). There was no genotype-phenotype correlation between the mutations identified and patients who underwent Kasai.
  
  
  CONCLUSIONS
  These data suggest that the Kasai procedure, although appropriate for children with biliary atresia, does not benefit children with AGS and actually appears to worsen outcome. The current data suggest that the Kasai is not a marker for underlying severe liver disease, but the procedure itself may have a detrimental effect on outcome. An appropriate medical evaluation and particular consideration of AGS is essential before surgical referral in infants with high GGT cholestasis.
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Kaye
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Rand
authors.forename: Pedro S
authors.initials: PS
authors.lastname: Munoz
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Alan W
authors.initials: AW
authors.lastname: Flake
authors.forename: Binita M
authors.initials: BM
authors.lastname: Kamath
mesh_terms: D016738:Alagille Syndrome / Q000150:complications / Q000401:mortality / Q000601:surgery*; D001663:Bilirubin / Q000097:blood; D002135:Calcium-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D005838:Genotype; D006331:Heart Diseases; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D007565:Jaundice / Q000209:etiology; D008099:Liver / Q000201:enzymology / Q000601:surgery*; D016031:Liver Transplantation / Q000706:statistics & numerical data; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011171:Portoenterostomy, Hepatic / Q000379:methods* / Q000401:mortality; D011183:Postoperative Complications / Q000401:mortality; D012189:Retrospective Studies; D000072099:Serrate-Jagged Proteins; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins; D005723:gamma-Glutamyltransferase; D001663:Bilirubin