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Factors Determining δ-Bilirubin Levels in Infants With Biliary Atresia
Wen Ye1, Philip Rosenthal, John C Magee
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.
Insights
Serum delta-bilirubin (Bδ) levels in infants with biliary atresia increase with conjugated bilirubin (Bc) and prolonged cholestasis. This finding aids in diagnosing and managing cholestasis in infants.
Area of Science:
- Biochemistry
- Pediatric Gastroenterology
- Neonatology
Background:
- Delta-bilirubin (Bδ) is formed via nonenzymatic transesterification of bilirubin conjugates with albumin in cholestasis.
- Infants with biliary atresia, a form of neonatal cholestasis, exhibit detectable Bδ levels.
Purpose of the Study:
- To investigate factors influencing serum Bδ concentrations in infants diagnosed with biliary atresia.
- To establish correlations between Bδ levels and other bilirubin analytes and cholestasis duration.
Main Methods:
- Prospective study (PROBE) enrollment of infants with biliary atresia.
- Analysis of concurrently measured serum bilirubin analytes: total bilirubin (TB), conjugated bilirubin (Bc), and unconjugated bilirubin.
- Application of graphical methods and a linear mixed-effects model to assess Bδ variability.
Main Results:
- Serum Bδ levels demonstrated a positive correlation with increasing conjugated bilirubin (Bc) and total bilirubin (TB).
- The duration of cholestasis was a significant determinant of Bδ levels, with each 100-day increase associated with a 1.0 mg/dL rise in Bδ (P < 0.0001).
- Serum albumin levels did not show a significant association with Bδ concentrations (P = 0.89).
Conclusions:
- Elevated Bδ levels in infants with biliary atresia are linked to higher Bc concentrations and longer cholestasis duration.
- Understanding the interrelationships between Bδ, Bc, TB, and direct-reacting bilirubin aids in assessing cholestasis severity.
- This knowledge supports improved diagnosis and clinical management strategies for infants and children with biliary atresia.
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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