A clinical staging system for SDB based on palate position, tonsil size, and body mass index is presented. It appears to be a valuable predictor of the success of UPPP. Additional studies and wider use of the staging system will ultimately define its role in the treatment of SDB.

Objectives To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia (BA) as a biomarker predictive of clinical sequelae of liver disease in the first two years of life. Study design Infants with BA undergoing HPE between June 2004-January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplant (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB<2.0, all others = TB≥2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. Results Fifty percent (68/137) of infants had TB<2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB<2.0 group vs. TB≥2 (86% vs. 20%, p<0.0001). Infants with TB≥2 had diminished weight gain (p<0.0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9–14.1, p<0.0001), hypoalbuminemia (OR 7.6, 95% CI 3.2–17.7, p< 0.0001), coagulopathy (OR 10.8, 95% CI 3.1–38.2, p=0.0002), LT (OR 12.4, 95% CI 5.3–28.7, p<0.0001), or LT or death (OR 16.8, 95% CI 7.2–39.2, p<0.0001). Conclusions Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes.

Biliary atresia (BA) is notable for marked ductular reaction and rapid development of fibrosis. Activation of the Hedgehog (Hh) pathway promotes the expansion of populations of immature epithelial cells that coexpress mesenchymal markers and may be profibrogenic. We examined the hypothesis that in BA excessive Hh activation impedes ductular morphogenesis and enhances fibrogenesis by promoting accumulation of immature ductular cells with a mesenchymal phenotype. Livers and remnant extrahepatic ducts from BA patients were evaluated by quantitative reverse‐transcription polymerase chain reaction (QRT‐PCR) and immunostaining for Hh ligands, target genes, and markers of mesenchymal cells or ductular progenitors. Findings were compared to children with genetic cholestatic disease, age‐matched deceased donor controls, and adult controls. Ductular cells isolated from adult rats with and without bile duct ligation were incubated with Hh ligand‐enriched medium ± Hh‐neutralizing antibody to determine direct effects of Hh ligands on epithelial to mesenchymal transition (EMT) marker expression. Livers from pediatric controls showed greater innate Hh activation than adult controls. In children with BA, both intra‐ and extrahepatic ductular cells demonstrated striking up‐regulation of Hh ligand production and increased expression of Hh target genes. Excessive accumulation of Hh‐producing cells and Hh‐responsive cells also occurred in other infantile cholestatic diseases. Further analysis of the BA samples demonstrated that immature ductular cells with a mesenchymal phenotype were Hh‐responsive. Treating immature ductular cells with Hh ligand‐enriched medium induced mesenchymal genes; neutralizing Hh ligands inhibited this. Conclusion: BA is characterized by excessive Hh pathway activity, which stimulates biliary EMT and may contribute to biliary dysmorphogenesis. Other cholestatic diseases show similar activation, suggesting that this is a common response to cholestatic injury in infancy. (HEPATOLOGY 2011;)