hyperbilirubinemia

Hyperbilirubinemia is an elevation of bilirubin in the bloodstream, often presenting with jaundice. Bilirubin is produced during heme breakdown from aged red blood cells. Unconjugated bilirubin is fat-soluble and carried to the liver bound to albumin, where it is conjugated by UDP-glucuronosyltransferase to become direct (conjugated) bilirubin, which is water-soluble and excreted in bile. A portion of conjugated bilirubin may be excreted in urine, and some is reabsorbed.

Causes are commonly categorized as prehepatic, hepatic, or posthepatic. Prehepatic causes include increased bilirubin production from hemolysis. Hepatic causes involve impaired conjugation or hepatocellular injury such as hepatitis, cirrhosis, or drug effects. Posthepatic causes result from biliary obstruction due to stones, tumors, or strictures. In newborns, physiologic jaundice, breastfeeding jaundice, or hemolytic disease can lead to hyperbilirubinemia. The pattern of elevation (predominantly unconjugated vs predominantly conjugated) helps narrow the likely mechanism.

Clinical features include yellowing of the skin and eyes, with dark urine and pale stools in cholestatic or obstructive cases. Assessment typically begins with measuring total and direct bilirubin, followed by fractionation into indirect (unconjugated) and direct (conjugated) bilirubin. Additional tests—complete blood count, reticulocyte count, liver enzymes, coagulation studies, and imaging such as ultrasound or MRCP—aid in identifying the underlying cause.

Management focuses on treating the underlying condition. In neonates, phototherapy reduces bilirubin levels, and exchange transfusion is used for severe cases. In adults, management targets the cause (hemolysis, hepatitis, biliary obstruction) and may include medical therapy, biliary drainage, or surgery. Prognosis depends on the etiology and the timeliness of treatment.