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Hyperbilirubinemia

  • Toshinori Kamisako
  • Masaki Iwai
  • Wilson M. S. TsuiEmail author
Chapter

Abstract

Hyperbilirubinemia is a disorder in the metabolism of bilirubin and is classified into unconjugated and conjugated hyperbilirubinemia.

Increases in serum UCB concentration can be due to an increase in the rate of the production of bilirubin, a decrease in uptake of bilirubin to hepatocytes, or a decrease in conjugation by UGT1A1. Non-hemolytic unconjugated hyperbilirubinemia caused by the mutations in UGT1A1 is classified into Crigler-Najjar syndrome type 1, Crigler-Najjar syndrome type 2, or Gilbert’s syndrome. Histological findings of liver biopsy are almost normal in these syndromes.

Most conjugated hyperbilirubinemia syndromes are caused by hepatobiliary disease, and the rest are caused by rare constitutional jaundice (Dubin-Johnson syndrome or Rotor syndrome). Reduced hepatic bilirubin clearance can be due to defective bilirubin excretion into bile in Dubin-Johnson syndrome and conjugated bilirubin reuptake in Rotor syndrome. Greenish black liver is observed in Dubin-Johnson syndrome. This is due to the presence of pigment within hepatocyte lysosome. The laparoscopic findings and histology of Rotor syndrome are normal.

The hereditary defects of three ABC transporters have been linked to several hepatobiliary disorders, ranging from the severe form of progressive familial intrahepatic cholestasis (PFIC) to the mild form of benign recurrent intrahepatic cholestasis (BRIC) and intrahepatic cholestasis of pregnancy (ICP). These are the result of mutations in the ATP8B1 (PFIC type 1), ABCB11 (PFIC type 2), and ABCB4 (PFIC type 3) genes. Liver biopsy from patients with PFIC types 1, 2, and 3 shows canalicular cholestasis with abnormal bile duct epithelium in the early stages of the diseases, and biliary cirrhosis in later phase.

Keywords

Hyperbilirubinemia Crigler-Najjar syndrome type 1 Crigler-Najjar syndrome type 2 Gilbert’s syndrome Dubin-Johnson syndrome Rotor syndrome Progressive familial intrahepatic cholestasis (PFIC). 

Abbreviations

ABC

ATP-binding cassette

BDG

Bilirubin diglucuronide

BMG

Bilirubin monoglucuronides

BRIC

Benign recurrent intrahepatic cholestasis

GST

Glutathione-S-transferase

ICP

Intrahepatic cholestasis of pregnancy

MRP2

Multidrug resistance-related protein 2

OATP

Organic anion transporting polypeptides

PFIC

Progressive familial intrahepatic cholestasis

TJP

Tight junction protein

UCB

Unconjugated bilirubin

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Toshinori Kamisako
    • 1
  • Masaki Iwai
    • 2
  • Wilson M. S. Tsui
    • 3
    Email author
  1. 1.OsakaJapan
  2. 2.KyotoJapan
  3. 3.Hong KongChina

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