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Objective: Alpha-1-antitrypsin (A1AT) deficiency is the most common genetic cause of liver disease in children; however, the role of polymorphic heterogeneity in the A1AT gene as a modifier of other forms of pediatric liver disease is not clear. We hypothesized that non-M A1AT allele variants are more common in children with chronic liver disease than in the general population., Methods: A retrospective, single-center study was performed in which A1AT phenotypes were obtained by reviewing charts of children with chronic liver disease. Chi-square analysis was used to compare allele frequencies in the population of children with liver disease with published epidemiologic data and to compare allele frequencies among disease subgroups., Results: The frequency of A1AT Z and other alleles was increased in children with chronic liver disease (n = 241) when compared with the published reference database (P < 0.001). This increase remained significant when the population was divided into disease subsets: biliary atresia (n = 67) and other liver disease (n = 174) (P < 0.001 for both). Among children with biliary atresia referred for liver transplant evaluation, the presence of a non-M allele was associated with a lower mean age at transplant listing than the MM phenotype (235 vs 779 days, P = 0.036) and more frequent loss of native liver by 24 months of age (90% vs 65%, P = 0.04)., Conclusions: A1AT non-M alleles are more frequent in children with chronic liver disease than in the general population. We speculate that these non-M alleles may act as genetic modifiers in pediatric liver disease in general and modulate disease progression in children with biliary atresia in particular.

Background: Chronic intrahepatic cholestasis is associated with severe pruritus that is often refractory to maximal medical management and leads to significantly impaired quality of life. The hypothesis in this study was that partial external biliary diversion (PEBD) can substantially improve intractable pruritus secondary to intrahepatic cholestasis with subsequent improvement of functional quality of life., Methods: Parents' and/or patients' clinical rating of pruritus, growth percentiles, biochemical parameters, and liver biopsies performed before and after surgery were compared in a retrospective medical record review., Results: Eight children underwent PEBD from 1990 through 1997. Complete follow-up data were available for seven patients. Before surgery, all patients had intense pruritus, which was not responsive to maximal medical therapy. Specimens obtained in preoperative liver biopsies showed moderate (n = 1), minimal (n = 6), or no (n = 1) portal fibrosis. After PEBD, all patients received ursodeoxycholic acid (10-15 mg/kg/dose two to three times daily) until resolution of pruritus. Of the seven patients with complete follow-up data, six had complete resolution of pruritus and sustained resolution up to 8 years after surgery. The patient with mild to moderate residual pruritus was the youngest to undergo PEBD. Growth improved from below the 5th percentile before surgery to the 5th through the 25th percentiles for five of six patients with more than 6 years' follow-up. All families reported improved quality of life, defined by school attendance and ability to resume normal activity with peers. There has been no clinical evidence of progression of liver disease., Conclusion: Partial external biliary diversion is effective in the long-term treatment of pruritus refractory to medical therapy and provides a favorable outcome in a select group of patients with chronic intrahepatic cholestasis without cirrhosis.

We report five infants in whom antenatal diagnosis of choledochal cyst was established by ultrasonography, and we review the seven previously reported cases. All but one infant had cystic dilatation of the common bile duct (type 1 cysts), and all infants were diagnosed during the second or third trimester. Eight of 12 infants (67%) developed jaundice in the first few days of life, but only 25% had a palpable abdominal mass. Seven of nine infants (78%) demonstrated complete obstruction of the distal common bile duct on intraoperative cholangiography. Liver histology was available for six patients. Five of six had cirrhosis or fibrosis with bile duct proliferation. All of the infants with fibrosis or cirrhosis had distal common bile duct obstruction. Despite liver biopsy findings of extensive fibrosis plus ascites with failure to thrive in one of our patients, all five patients demonstrated clinical and biochemical improvement following surgical excision and porto- or choledochoenterostomy. All were free of symptoms by 6 months of age. Congenital choledochal cyst should be considered in the differential diagnosis of any sonolucent abdominal mass of the fetus. Neonates with distal common bile duct obstruction and fibrosis in association with presumed choledochal cyst should have prompt surgical exploration, intraoperative cholangiography, and close postoperative follow-up. The long-term outcome with prompt surgical correction is excellent.