From the Guidelines
Hyperbilirubinemia is primarily caused by excessive bilirubin in the blood, resulting from increased production, decreased liver uptake, impaired conjugation, or reduced excretion, with common causes including hemolytic disorders, liver diseases, and biliary obstruction, as noted in the most recent study 1. The metabolism of bilirubin can be divided into prehepatic, intrahepatic, and posthepatic phases, with each phase having distinct causes of hyperbilirubinemia.
- Prehepatic causes include hemolysis or absorption of a large hematoma, related to increased heme production in hemolytic anemias, such as sickle cell disease, thalassemia, hereditary spherocytosis, and glucose-6-phosphate dehydrogenase deficiency, as stated in 1.
- Intrahepatic causes involve errors in enzyme metabolism in the hepatocytes, such as Gilbert syndrome, which affects 5% of the American population and leads to a transient increase in unconjugated bilirubin levels, as mentioned in 1.
- Posthepatic causes include biliary obstruction from gallstones or tumors, which prevents bilirubin excretion, as well as certain medications that can interfere with bilirubin metabolism, such as acetaminophen, penicillin, and oral contraceptives, as noted in 1. Management of hyperbilirubinemia depends on the underlying cause and may include treating infections, addressing hemolytic disorders, removing obstructions, or discontinuing problematic medications, with severe cases potentially requiring phototherapy or exchange transfusions to prevent kernicterus and neurological damage, as implied by the studies 1.
From the Research
Causes of Hyperbilirubinemia
- Hemolysis is a significant factor in the development of hyperbilirubinemia, particularly in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency 2, 3, 4
- G6PD deficiency is a common enzyme deficiency that affects over 300 million people worldwide and can lead to extreme neonatal hyperbilirubinemia 2, 3, 4
- Oxidative stress can trigger hemolysis in individuals with G6PD deficiency, leading to hyperbilirubinemia 3, 4
- Disruption of the oxidant-antioxidant balance and impaired recycling of peroxiredoxin 2 may also contribute to the development of hyperbilirubinemia in individuals with G6PD deficiency 3
- Hepatitis A infection can also cause hemolysis and hyperbilirubinemia, particularly in individuals with G6PD deficiency 5
- Liver dysfunction or disease can lead to an inability to properly metabolize or excrete bilirubin, resulting in hyperbilirubinemia 6
Risk Factors
- G6PD deficiency is a significant risk factor for hyperbilirubinemia, particularly in neonates 2, 3, 4
- Infection, such as hepatitis A, can trigger hemolysis and hyperbilirubinemia in individuals with G6PD deficiency 5
- Certain medications, such as primaquine and rasburicase, can trigger hemolysis and hyperbilirubinemia in individuals with G6PD deficiency 4
- Fava bean ingestion can also trigger hemolysis and hyperbilirubinemia in individuals with G6PD deficiency 4