Enterohepatic circulation of bilirubin (Bilirubin EHC)

The enterohepatic circulation of bilirubin is a biological pathway involving the movement of bilirubin from the liver to the small intestine via bile and its subsequent reabsorption back into the systemic circulation [1, 12]. In the liver, unconjugated (indirect) bilirubin is converted into conjugated (direct) bilirubin by the enzyme UGT1A1 to facilitate excretion into the bile [7, 13]. Once in the intestinal lumen, bacterial enzymes such as beta-glucuronidase deconjugate the bilirubin back into its indirect, lipid-soluble form, allowing it to be reabsorbed through the intestinal epithelium [4, 12]. This recycling mechanism is a significant factor in neonatal hyperbilirubinemia, where high levels of indirect bilirubin can lead to neurotoxicity or kernicterus [5, 8]. Pharmacological interventions often target this cycle by using binding agents like oral agar, calcium salts, or zinc sulfate, which precipitate or sequester bilirubin in the gut to enhance fecal excretion [3, 6, 11]. Modulating this pathway is a critical therapeutic approach for managing conditions characterized by impaired bilirubin metabolism or clearance, such as Crigler-Najjar and Gilbert syndromes [6, 9].

Other names

Enterohepatic cycle of indirect bilirubinBilirubin recyclingEnterohepatic circulation of unconjugated bilirubinBilirubin enterohepatic cycle

Intervention involves inhibiting the intestinal reabsorption of unconjugated bilirubin by physical binding, precipitation in the gut lumen, or increasing gastrointestinal transit speed to reduce systemic bilirubin levels.