From the Guidelines
Elevated bilirubin is a sign of an underlying medical condition, such as liver dysfunction, hemolysis, or bile duct obstruction, which requires prompt medical evaluation to determine the cause and appropriate treatment. Bilirubin is a by-product of the breakdown of haemoglobin by the reticuloendothelial system, and it exists in two forms: unconjugated and conjugated 1. The most common cause of an isolated elevated bilirubin concentration is Gilbert’s syndrome, an inherited disorder of metabolism that leads to impaired conjugation via reduced activity of the enzyme glucuronyltransferase 1.
Key Points to Consider
- Elevated bilirubin can result from various conditions, including liver diseases like hepatitis or cirrhosis, bile duct obstructions, certain genetic disorders like Gilbert's syndrome, or hemolytic anemias where red blood cells break down too quickly 1.
- The significance of elevated bilirubin depends on whether it's primarily unconjugated (pre-liver processing) or conjugated (post-liver processing), which helps determine the underlying cause 1.
- If the majority of the elevated bilirubin comprises the unconjugated fraction, then the cause, in the absence of haemolysis, is virtually always Gilbert’s syndrome, and such individuals should be fully reassured 1.
- In neonates and infants, a physiological increase in total bilirubin, which is unconjugated, may be pathological if high or prolonged, and referral to a paediatrician for urgent assessment of possible liver disease is essential if the conjugated bilirubin is >25 μmol/L 1.
Importance of Medical Evaluation
Medical evaluation is necessary to identify the cause of elevated bilirubin, as treatment depends entirely on the underlying condition rather than treating the bilirubin level itself 1. During evaluation, your doctor may order additional liver function tests, imaging studies, or other diagnostics to determine the appropriate course of action. Prompt medical attention is crucial to prevent potential complications and improve patient outcomes.
From the Research
Definition of Hyperbilirubinemia
- Hyperbilirubinemia, also known as elevated bilirubin, is a condition where the liver is unable to properly metabolize or excrete bilirubin, resulting in an excess of bilirubin in the blood 2.
- This condition is often indicated by jaundice, a physical finding that occurs when bilirubin levels exceed 3 mg/dL 3.
- Hyperbilirubinemia can be caused by various factors, including excess bilirubin production, impaired liver uptake, impaired conjugation, and bile clearance defects 4.
Causes and Diagnosis
- The causes of hyperbilirubinemia can be diverse, ranging from alcoholic liver disease, biliary strictures, choledocholithiasis, drug-induced liver injury, hemolysis, or hepatitis 3.
- Diagnosis of hyperbilirubinemia typically involves a comprehensive medical history, review of systems, and physical examination, followed by laboratory tests and imaging assessments 3.
- Laboratory tests may include assays for bilirubin (total and fractionated), complete blood cell count, aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, alkaline phosphatase, albumin, prothrombin time, and international normalized ratio 3.
Clinical Significance
- Elevated plasma bilirubin levels can be a frequent clinical finding, and it is essential to assess alterations in bilirubin concentrations in relation to patient anamnesis, the degree of the alteration, and the pattern of concurrent biochemical alterations 4.
- Hyperbilirubinemia can be a predictor of common bile duct stones in acute cholecystitis and symptomatic cholelithiasis, and trends in total bilirubin can be used to guide testing for the presence of common bile duct stones 5.
- In newborn infants, unconjugated hyperbilirubinemia is common, but rare later in life, and numerous variables related to nutrition, ethnicity, and genetic variants can impact bilirubin metabolism 6.