Distribution of serum bilirubin conjugates in pediatric hepatobiliary diseases

Rosenthal, Philip; Henton, Donaby; Felber, Sharon; Sinatra, Frank

doi:10.1016/s0022-3476(87)80154-3

Cited by 14 publications

(14 citation statements)

References 10 publications

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“…Measurement of serum conjugated bilirubin fractions have been used as a minimally invasive method of assessing bilirubin conjugation in neonates, 15,24,25 children, 26,27 and adults, 12,28 alike. It is recognized that physiologically, a small fraction of bilirubin conjugates effluxes from the hepatocyte to the serum.…”

Section: Discussionmentioning

confidence: 99%

Imbalance Between Production and Conjugation of Bilirubin: A Fundamental Concept in the Mechanism of Neonatal Jaundice

et al. 2002

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ABSTRACT. Objective. The objective of this study was to evaluate the roles of production and conjugation of bilirubin, individually and in combination, in the mechanism of neonatal jaundice.Methods. A cohort of healthy, term male newborns was sampled on the third day of life, coincident with routine metabolic screening, for blood carboxyhemoglobin determination, a reflection of heme catabolism, and for serum unconjugated and conjugated bilirubin fractions, reflecting bilirubin conjugation. The former was determined by gas chromatography, corrected for inspired CO (COHbc), and expressed as percentage of total hemoglobin. Serum bilirubin fractions were quantified by alkaline methanolysis and reverse phase high performance liquid chromatography. The sum of all bilirubin fractions comprised serum total bilirubin (STB). Conclusions. Within the range of STB concentrations encountered, both increasing bilirubin production and diminishing bilirubin conjugation contributed to STB. The production/conjugation index confirmed that imbalance between production and conjugation of bilirubin plays an important role in the mechanism of neonatal bilirubinemia. Pediatrics 2002;110(4). URL: http://www. pediatrics.org/cgi/content/full/110/4/e47; alkaline methanolysis, bilirubin, bilirubin conjugation, carbon monoxide, carboxyhemoglobin, gas chromatography, hemolysis, high performance liquid chromatography, physiologic jaundice. Total conjugated bilirubin (TCB) was comprised of the sum of the conjugated fractions and was expressed as percentage of STB (TCB[%]). A "bilirubin production/conjugation index" (COHbc/[TCB(%)]ABBREVIATIONS. STB, serum total bilirubin; CO, carbon monoxide; COHb, carboxyhemoglobin; COHbc, COHb corrected for inspired CO; UGT, uridine diphosphoglucuronate glucuronosyltransferase 1A1; G-6-PD, glucose-6-phosphate dehydrogenase; TCB, serum total conjugated bilirubin. J aundice is common during the first days of postnatal life and affects almost two thirds of human newborns. The mechanism of this bilirubinemia is multifactorial, as recently summarized, and comprises primarily processes contributing to increased bilirubin load, or diminished bilirubin clearance. 1,2 The former may be the result of factors that augment bilirubin production and the enterohepatic circulation, whereas the latter is primarily the result of immature conjugative capacity, although impaired hepatic uptake or excretion may also play a part. It has been suggested that serum total bilirubin (STB) concentrations that remain within the physiologic range result from equilibrium between bilirubin production and elimination. In contrast, in some neonates, imbalance between these processes may occur, with bilirubin production being relatively higher than conjugation. This imbalance is thought to result in hyperbilirubinemia. 3 Assessment of the role of hemolysis may be accomplished through assessment of endogenous carbon monoxide (CO) production by accurately measuring blood carboxyhemoglobin (COHb), or end tidal CO, both with correction for ambient ...

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Section: Discussionmentioning

confidence: 99%

Imbalance Between Production and Conjugation of Bilirubin: A Fundamental Concept in the Mechanism of Neonatal Jaundice

et al. 2002

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“…Some studies have encompassed larger numbers of patients, but with an array of disorders including hemolysis, Gilbert syndrome, and hepatobiliary disease (8, 9, 14). None of the previous reports investigated a single population with a single disease as this study did.…”

Section: Discussionmentioning

confidence: 99%

“…As this only occurs when Bc is present in excess, significant amounts of circulating Bδ are only observed in patients with cholestasis. In studies involving children it was found that Bδ insignificantly contributed to TB in patients with predominantly Bu and in infants a month old or less; whereas, Bδ may contribute over 50% of TB in older children with cholestasis (8, 9). …”

Section: Introductionmentioning

confidence: 99%

Factors Determining δ‐Bilirubin Levels in Infants With Biliary Atresia

Rosenthal

Magee

et al. 2015

J. pediatr. gastroenterol. nutr.

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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.

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“…Because the liver is the only organ that can esterify bilirubin to any significant extent and conjugated bilirubin compounds are not absorbed from the bowel, in the absence of hepatocellular disease or cholestasis, the profile is believed to reflect the intrahepatocytic bilirubin profile. This method has been used in the minimally invasive assessment of bilirubin conjugation in neonates, [42][43][44] children, 45,46 and adults 21,33 alike.…”

Section: Discussionmentioning

confidence: 99%