Effect of Kasai Procedure on Hepatic Outcome in Alagille Syndrome
ABSTRACT 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.
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.
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.
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.
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ABSTRACT: A 1-year-old girl had pancreaticobiliary maljunction, a choledochal cyst, and polycystic kidney. At the age of 4 years, she was treated by resection of the choledochal cyst and Roux-en-Y reconstruction because of the cyst's risk of cancer. She was diagnosed as having congenital hepatic fibrosis based on the histological findings. Postoperatively, she suffered recurrent fever of unknown origin, refractory to several antibiotics. At the age of 6 years, she underwent living donor liver transplantation from her father. Multi-drug-resistant Pseudomonas aeruginosa was cultured in the recipient's liver. After liver transplantation, she had no episodes of recurrent fever. Roux-en-Y reconstruction should be avoided for ductal plate malformations such as congenital hepatic fibrosis.06/2013; 1(1):43-5. DOI:10.1055/s-0033-1341420
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ABSTRACT: Alagille syndrome (AGS) is an autosomal dominant disorder of chronic cholestasis characterized by paucity of interlobular bile ducts. The condition has been described only as isolated case reports in India. We describe clinical profile and outcome of nine subjects (six infants and three older children) with AGS. Cholestasis and characteristic facies were present in all, followed by congenital heart disease, vertebral anomalies, and posterior embryotoxon in seven, five, and four cases, respectively. Pruritus was the commonest symptom which was refractory to medical treatment in one third of cases. Two cases developed decompensated liver disease on follow up. High index of suspicion for this multisystemic condition is essential for correct diagnosis and management.Indian Journal of Gastroenterology 09/2013; DOI:10.1007/s12664-013-0392-4
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ABSTRACT: Alagille syndrome is a multisystem disorder with an autosomic dominant pattern of inheritance that affects the liver, heart, eyes, kidneys, skeletal system and presents characteristic facial features. Mutations of the JAG1 gene have been identified in 20–89% of the patients with Alagille syndrome, this gene encodes for a ligand that activates the Notch signaling pathway. In the present study we analyzed 9 Mexican patients with Alagille syndrome who presented the clinical criteria for the classical presentation of the disease. By using the denaturing high performance liquid chromatography mutation analysis we were able to identify different mutations in 7 of the patients (77.77%), importantly, we found 5 novel mutations in JAG1 gene. The allelic frequency distribution of 13 polymorphisms in Mexican population is also reported. The overall results demonstrated an expanding mutational spectrum of JAG1 gene in the Mexican population.12/2014; 2. DOI:10.1016/j.mgene.2013.10.002