Inherited Disorders of Bilirubin Transport and Conjugation: New Insights Into Molecular Mechanisms and Consequences

Erlinger, S; Arias, Irwin M.; Dhumeaux, Daniel

doi:10.1053/j.gastro.2014.03.047

Cited by 202 publications

(205 citation statements)

References 124 publications

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“…The data are in line with the observation that patients treated with octreotide can experience hyperbilirubinemia (Arosio et al, 1988;Crook and Steger, 2001;Koren et al, 2013). Bilirubin is taken up into hepatocytes in part by a carriermediated process involving OATPs 1B1, 1B3, and 2B1 (KullakUblick et al, 2001;Stieger et al, 2012), is rapidly conjugated to bilirubin glucuronides by uridine diphosphate-glucuronosyl transferase (Erlinger et al, 2014), and is then excreted from hepatocytes into bile canaliculi by the multidrug resistanceassociated protein 2 (MRP2) (Kamisako et al, 1999).…”

Section: Discussionsupporting

confidence: 63%

Octreotide Inhibits the Bilirubin Carriers Organic Anion Transporting Polypeptides 1B1 and 1B3 and the Multidrug Resistance-Associated Protein 2

Visentin

Stieger

Merz

et al. 2015

J Pharmacol Exp Ther

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The somatostatin analog octreotide can lead to hyperbilirubinemia without evidence of liver injury. Here we investigate whether octreotide inhibits the main sinusoidal/canalicular bilirubin carriers and whether it is a transport substrate. Octreotide showed the most potent inhibitory effect toward OATP1B1-mediated transport and weaker inhibition for OATP1B3-and MRP2-mediated transport. Octreotide had no effect on OATP2B1-mediated transport. Octreotide inhibited [ Uptake of radiolabeled octreotide by OATP1B1-CHO cells was higher than in wild-type CHO cells and nonlabeled octreotide at the extracellular compartment was able to transstimulate the OATP1B1-mediated efflux of intracellular [ 3 H]E17bG, suggesting that octreotide is a substrate of OATP1B1. In summary, this study shows interaction of octreotide on the human hepatocellular bilirubin transporters OATP1B1, OATP1B3, and MRP2, notably OATP1B1. These findings are in line with the clinical observation that a fraction of patients under treatment with octreotide exhibit hyperbilirubinemia.

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Section: Discussionsupporting

confidence: 63%

Octreotide Inhibits the Bilirubin Carriers Organic Anion Transporting Polypeptides 1B1 and 1B3 and the Multidrug Resistance-Associated Protein 2

Visentin

Stieger

Merz

et al. 2015

J Pharmacol Exp Ther

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“…Auch Behandlungsversuche mithilfe der Leber-bzw. Hepatozytentransplantation wurden beschrieben [26,27].…”

Section: Primäre Störungen Des Bilirubinstoffwechselsunclassified

“…Die Diagnostik wird molekulargenetisch geführt (UDP-GT1-A1-Promotor-Polymorphismus). Bei dieser milderen Form wird die tägliche Gabe von Phenobarbital empfohlen [27].…”

Section: Typ IIunclassified

“…Aufgrund der gefürchteten Komplikation des Kernikterus muss v. a. beim Neugeborenen rasch diagnostisch differenziert werden, ob eine schwere (indirekte) Hyperbilirubinämie mit entsprechendem Handlungsbedarf vorliegt. Generell sollte man die "Hyperbilirubinämiesyndrome" differenzialdiagnostisch insofern stets in Betracht ziehen, als ihre Diagnose unnötige invasivere Untersuchungen zum Ausschluss einer vermuteten schweren hepatobiliären Erkrankung vermeiden hilft [27]. …”

Section: Ausblickunclassified

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Indirekte Hyperbilirubinämie

Hauer

2017

Monatsschr Kinderheilkd

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“…Other than these findings, normal physical examination, lab exams and imaging studies are the rule, and when biopsy is taken, a normal histopathological liver parenchyma is usually seen (16).…”

Section: Discussionmentioning

confidence: 99%

Unusual presentation of Gilbert disease with high levels of unconjugated bilirubin. Report of two cases

et al. 2015

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Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events, bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dl in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases.

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Inherited Disorders of Bilirubin Transport and Conjugation: New Insights Into Molecular Mechanisms and Consequences

Cited by 202 publications

References 124 publications

Octreotide Inhibits the Bilirubin Carriers Organic Anion Transporting Polypeptides 1B1 and 1B3 and the Multidrug Resistance-Associated Protein 2

Octreotide Inhibits the Bilirubin Carriers Organic Anion Transporting Polypeptides 1B1 and 1B3 and the Multidrug Resistance-Associated Protein 2

Indirekte Hyperbilirubinämie

Unusual presentation of Gilbert disease with high levels of unconjugated bilirubin. Report of two cases

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