Effect of Kasai Procedure on Hepatic Outcome in Alagille Syndrome

Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Journal of pediatric gastroenterology and nutrition (Impact Factor: 2.63). 09/2010; 51(3):319-21. DOI: 10.1097/MPG.0b013e3181df5fd8
Source: PubMed


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.

34 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biliary diseases in children are infrequent; however, they can be associated with high morbidity and mortality if an accurate diagnosis is not made and adequate treatment provided in a timely fashion. Biliary atresia, choledochal cysts, gallbladder disease, and Alagille syndrome can be associated with similar clinical symptoms, laboratory findings, and radiographic findings, which makes accurate diagnosis difficult. The correct treatment for each of these clinical entities is different and can significantly reduce morbidity and mortality from these diseases. In this article, we discuss the epidemiology, approach to diagnosis, prognosis, and treatment modalities for these four disease processes.
    No preview · Article · Apr 2011 · Current Gastroenterology Reports
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is a multisystem disorder due to defects in components of the Notch signalling pathway, most commonly due to mutation in JAG1 (ALGS type 1), but in a small proportion of cases mutation in NOTCH2 (ALGS type 2). The main clinical and pathological features are chronic cholestasis due to paucity of intrahepatic bile ducts, peripheral pulmonary artery stenosis, minor vertebral segmentation anomalies, characteristic facies, posterior embryotoxon/anterior segment abnormalities, pigmentary retinopathy, and dysplastic kidneys. It follows autosomal dominant inheritance, but reduced penetrance and variable expression are common in this disorder, and somatic/germline mosaicism may also be relatively frequent. This review discusses the clinical features of ALGS, including long-term complications, the clinical and molecular diagnosis, and management.
    Full-text · Article · Sep 2011 · European journal of human genetics: EJHG
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alagille syndrome (ALGS) is a multisystem disorder that manifests as childhood cholestasis. Reports of liver transplantation (LT) for patients with ALGS have come largely from single centers, which have reported survival rates of 57% to 79%. The aim of this study was to determine LT outcomes for patients with ALGS. We performed a retrospective analysis of the Studies of Pediatric Liver Transplantation database, which contains information about 3153 pediatric LT recipients. Data were available for 91 patients with ALGS and for 236 age-matched patients with biliary atresia (BA). The frequency of complex cardiac anomalies was lower in the LT group with ALGS versus published ALGS series (5% versus 13%). The pretransplant glomerular filtration rate (GFR) was <90 mL/minute/1.73 m(2) in 18% of the LT patients with ALGS and in 5% of the LT patients with BA (P < 0.001). The height deficit at listing was worse for the ALGS patients (66%) versus the BA patients (22%). The 1-year patient survival rates were 87% for the ALGS patients and 96% for the BA patients (P = 0.002). The deaths in the ALGS group mostly occurred within the first 30 days. No pretransplant factors associated with death were identified in the ALGS group. A survival analysis revealed that biliary (P = 0.02), vascular (P < 0.001), central nervous system (CNS; P < 0.001), and renal complications (P < 0.001) after LT were associated with death in the ALGS group. Renal insufficiency in the ALGS patients worsened after LT, and at 1 year, GFR was <90 mL/minute/1.73 m(2) in 22% of the LT patients with ALGS but in only 8% of the patients with BA (P = 0.0014). More LT pediatric patients with ALGS either were currently receiving special education (50% versus 30% for BA patients, P = 0.02) or had received special education in the past (60% versus 36%, P = 0.01). Vascular, CNS, and renal complications were increased in the ALGS patients after LT, and this reflected multisystem involvement. Although the 1-year survival rate was modestly lower for the ALGS patients versus the BA patients, the clustering of deaths within the first 30 days is notable and warrants increased vigilance and further investigation.
    Full-text · Article · Aug 2012 · Liver Transplantation
Show more