Factors Determining δ‐Bilirubin Levels in Infants With Biliary Atresia

Abstract

Background Delta bilirubin (Bδ) forms when bilirubin conjugates covalently bind to albumin by way of non-enzymatic transesterification in patients with cholestasis. Cholestatic infants with biliary atresia form Bδ. The aim of this study was to investigate the factors determining serum Bδ concentrations in infants with biliary atresia. Methods Study subjects were infants enrolled into 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 (Bu)) 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. One mg/dL increase 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 BA increase with increasing levels of Bc and longer duration of cholestasis. Understanding the relationship between Bδ, Bc, total bilirubin 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.

Can Free Carnitine or Bilirubin in Blood Be Used in Neonatal Screening for Biliary Atresia?

“…18 Neonatal hyperbilirubinemia with elevated UBIL can be treated by phototherapy or hemodialysis; if it is not diagnosed and treated on time, it can cause acute bilirubin encephalopathy, which leads to hearing loss, cerebral palsy, epilepsy, autism, and some sequelae. 19 Neonatal hyperbilirubinemia with elevated DB (BMG, BDG, or delta bilirubin) indicates a disorder of bile excretion, such as neonatal cholestasis, BA, 11,12,20,21 or indicates a bilirubin metabolic disease, such as Gilbert's syndrome. 22 If all forms of neonatal hyperbilirubinemia can be detected, diagnosed, and treated earlier, it will improve treatment results and decrease the occurrence of sequelae.…”

“…The American Academy of Pediatrics Subcommittee on hyperbilirubinemia and some units recommend that all newborns should be screened with transcutaneous bilirubin measurements, 23 which cannot distinguish hyperbilirubinemia type, or with total serum bilirubin and direct bilirubin measurement, which is the clinical laboratory method not suitable to mass screening. 11,12,21 Recently, we published a method to measure UBIL MS , BMG, BDG from the DBSs using MS/MS. 14 This method can be utilized for the screening of diseases in newborns by MS/MS and for the screening of various kind of hyperbilirubinemia.…”

Aggressive nutrition in extremely low birth weight infants: impact on parenteral nutrition associated cholestasis and growth

“…Conjugated bilirubin was measured by spectrophotometric quantitation (Vitros Chemistry System, Ortho Clinical Diagnostics, Raritan, NJ, USA). Parenteral nutrition associated cholestasis was defined as conjugated bilirubin >1.5 mg/dl (25 µmol/l) measured at two consecutive occasions ( Bines, 2004 ) which corresponds closely to >2 mg/dl direct bilirubin ( Ye et al, 2015 ). Conjugated bilirubin levels were used as they are more accurate compared to direct bilirubin ( Doumas & Wu, 1991 ), in particular when bilirubin levels rise and persist over a longer period of time ( Ye et al, 2015 ).…”

“…Parenteral nutrition associated cholestasis was defined as conjugated bilirubin >1.5 mg/dl (25 µmol/l) measured at two consecutive occasions ( Bines, 2004 ) which corresponds closely to >2 mg/dl direct bilirubin ( Ye et al, 2015 ). Conjugated bilirubin levels were used as they are more accurate compared to direct bilirubin ( Doumas & Wu, 1991 ), in particular when bilirubin levels rise and persist over a longer period of time ( Ye et al, 2015 ). NEC was diagnosed either clinically (modified Bell’s stage ≥ IIa ( Walsh & Kliegman, 1986 )) or after surgical exploration.…”

Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy

“…Considering these two endpoints together, a composite clinical outcome was defined as follows: If a patient had no liver transplant/death and serum bilirubin was <1.5 mg/dL at 360 days post‐HPE, then the patient was grouped into the Good Outcome group; otherwise, if a patient had liver transplant/death or serum bilirubin persisting above 1.5 mg/dL up to 360 days post‐HPE, then the patient was grouped into the Poor Outcome group. Total bilirubin was determined directly using standard laboratory methods or calculated by the addition of direct plus indirect bilirubin . Total bilirubin levels after transplant were not used for the analysis.…”