From the Guidelines
Hyperbilirubinemia is primarily caused by an imbalance between bilirubin production and clearance, which can be attributed to various factors including hemolytic diseases, liver dysfunction, and obstruction of bile flow, as well as physiological conditions such as neonatal jaundice. The aetiology of hyperbilirubinemia can be broadly categorized into unconjugated (indirect) and conjugated (direct) hyperbilirubinemia. Unconjugated hyperbilirubinemia is often seen in conditions like hemolytic anemias, ineffective erythropoiesis, Gilbert syndrome, and Crigler-Najjar syndrome, which either increase bilirubin production or impair the liver's ability to conjugate bilirubin 1. On the other hand, conjugated hyperbilirubinemia results from conditions that obstruct bile flow or damage hepatocytes, including viral hepatitis, alcoholic liver disease, drug-induced liver injury, primary biliary cholangitis, primary sclerosing cholangitis, and biliary obstruction from gallstones or tumors.
Causes of Hyperbilirubinemia
- Hemolytic anemias: Conditions characterized by excessive red blood cell breakdown, leading to increased bilirubin production.
- Ineffective erythropoiesis: Disorders affecting the production of red blood cells, resulting in increased bilirubin levels.
- Gilbert syndrome and Crigler-Najjar syndrome: Genetic disorders impairing the liver's ability to conjugate bilirubin.
- Viral hepatitis, alcoholic liver disease, and drug-induced liver injury: Conditions causing hepatocyte damage and impairing bile flow.
- Primary biliary cholangitis, primary sclerosing cholangitis, and biliary obstruction: Conditions obstructing bile flow and leading to conjugated hyperbilirubinemia.
Diagnosis and Management
Diagnosis of hyperbilirubinemia typically involves liver function tests, complete blood count, and imaging studies to determine the specific cause. Management strategies vary depending on the underlying cause and may include phototherapy for neonatal jaundice, treatment of the primary condition in adults, and, in severe cases, exchange transfusion to prevent bilirubin encephalopathy (kernicterus) 1. Understanding the aetiology of hyperbilirubinemia is crucial for appropriate management and prevention of potential complications, such as kernicterus, especially in high-risk neonates. According to the most recent guidelines, phototherapy is an essential intervention for severe hyperbilirubinemia, especially in neonates at high risk, and its use reduces the risk of bilirubin neurotoxicity as well as the need for exchange transfusions 1.
From the Research
Aetiology of Hyperbilirubinaemia
The aetiology of hyperbilirubinaemia is a complex condition with various underlying causes. Some of the key factors include:
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is a common enzyme deficiency affecting more than 300 million individuals worldwide 2
- Hemolysis, which is an important pathogenetic factor in G6PD deficiency-associated neonatal hyperbilirubinemia 2
- Immaturity and ABO incompatibility, which can also contribute to the development of hyperbilirubinemia 3
Role of G6PD Deficiency
G6PD deficiency is a significant cause of severe indirect hyperbilirubinemia, prolonged jaundice, and bilirubin-induced encephalopathy in neonates 4. Studies have shown that G6PD-deficient neonates are at a higher risk of developing extreme hyperbilirubinemia, with its severe sequelae of bilirubin neurotoxicity and the potential of death 2.
Clinical Presentation and Course
The clinical presentation and course of G6PD-deficient neonates with hyperbilirubinemia can vary, but studies have shown that these neonates tend to have higher serum bilirubin levels and a greater need for exchange transfusion compared to non-G6PD deficient neonates 5. However, the time of onset of jaundice, reticulocyte count, hematocrit level, phototherapy duration, and duration of hospitalization may not differ significantly between G6PD-deficient and non-G6PD deficient neonates 5.
Emerging Therapies
Several emerging therapies are being investigated for the management of hyperbilirubinemia, including the use of tin mesoporphyrin and intravenous immunoglobulin, which may decrease the need for exchange transfusions 6. Additionally, the use of ursodeoxycholic acid (UDCA) has been shown to reduce the rate of readmission in G6PD-deficient neonates requiring phototherapy 4.