Wen Ye1, Philip Rosenthal, John C Magee, Peter F Whitington. 1. *Department of Biostatistics, University of Michigan, Ann Arbor †Departments of Pediatrics & Surgery, UCSF Benioff Children's Hospital, University of California, San Francisco ‡Department of Surgery, University of Michigan, Ann Arbor §Department of Pediatrics, Feinberg Medical School of Northwestern University, Ann & Robert H. Lurie Children's Hospital of Chicago, IL.
Abstract
OBJECTIVES: δ-Bilirubin (Bδ) forms when bilirubin conjugates covalently bind to albumin by way of nonenzymatic transesterification in patients with cholestasis. Infants with cholestasis with biliary atresia form Bδ. The aim of the present study was to investigate the factors determining serum Bδ concentrations in infants with biliary atresia. METHODS: Study patients were infants enrolled in a prospective study (PROBE: Clinicaltrials.gov NCT00061828) of biliary atresia. We acquired data of concurrently measured serum bilirubin analytes (total bilirubin [TB], conjugated bilirubin [Bc], and unconjugated bilirubin) and applied graphical methods and linear mixed effects model to study factors contributing to Bδ variability. RESULTS: Bδ level increased with increasing levels of Bc and TB. In addition, the length of time cholestasis persisted partially determined the level of Bδ. An increase of 1 mg/dL in Bc is related to approximately 0.36 mg/dL increase in Bδ (P < 0.0001); every 100 days of cholestasis is associated with an approximately 1.0 mg/dL increase in Bδ (P < 0.0001) given the same level of Bc. Serum albumin levels are not significantly related to Bδ (P = 0.89). CONCLUSIONS: Bδ levels in infants with biliary atresia increase with increasing levels of Bc and longer duration of cholestasis. Understanding the relation among Bδ, Bc, TB, and direct-reacting bilirubin levels can help in interpretation of the clinical extent of cholestasis in infants and children with biliary atresia, assisting in the diagnosis and management of these infants.
OBJECTIVES: δ-Bilirubin (Bδ) forms when bilirubin conjugates covalently bind to albumin by way of nonenzymatic transesterification in patients with cholestasis. Infants with cholestasis with biliary atresia form Bδ. The aim of the present study was to investigate the factors determining serum Bδ concentrations in infants with biliary atresia. METHODS: Study patients were infants enrolled in a prospective study (PROBE: Clinicaltrials.gov NCT00061828) of biliary atresia. We acquired data of concurrently measured serum bilirubin analytes (total bilirubin [TB], conjugated bilirubin [Bc], and unconjugated bilirubin) and applied graphical methods and linear mixed effects model to study factors contributing to Bδ variability. RESULTS: Bδ level increased with increasing levels of Bc and TB. In addition, the length of time cholestasis persisted partially determined the level of Bδ. An increase of 1 mg/dL in Bc is related to approximately 0.36 mg/dL increase in Bδ (P < 0.0001); every 100 days of cholestasis is associated with an approximately 1.0 mg/dL increase in Bδ (P < 0.0001) given the same level of Bc. Serum albumin levels are not significantly related to Bδ (P = 0.89). CONCLUSIONS: Bδ levels in infants with biliary atresia increase with increasing levels of Bc and longer duration of cholestasis. Understanding the relation among Bδ, Bc, TB, and direct-reacting bilirubin levels can help in interpretation of the clinical extent of cholestasis in infants and children with biliary atresia, assisting in the diagnosis and management of these infants.
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