The most common cause of hyperbilirubinemia is

• A. Cholelithiasis
• B. Hemolysis
• C. Acute Viral Hepatitis
• D. Gilbert Syndrome

Answer: (A)

A useful way to think about hyperbilirubinemia is to separate causes by whether bilirubin is raised in its unconjugated form or its conjugated form. The most common cause overall is Gilbert syndrome, a benign inherited condition that produces mild unconjugated (indirect) hyperbilirubinemia due to reduced activity of the liver enzyme UDP-glucuronosyltransferase (UGT1A1). Because the liver’s ability to conjugate bilirubin is slightly impaired, bilirubin builds up in its unconjugated form, and levels rise intermittently, often during fasting, illness, or stress. People with Gilbert syndrome typically have normal liver enzymes and only mild jaundice on occasion, and no treatment is needed.

This pattern differs from the other options: cholelithiasis can cause obstructive jaundice with a rise in direct (conjugated) bilirubin, but it’s not the most common cause of hyperbilirubinemia overall. Acute viral hepatitis raises bilirubin through hepatocellular injury and often increases both direct and indirect fractions. Hemolysis increases unconjugated bilirubin due to higher production, but it’s less common as a chronic, mild cause compared with Gilbert syndrome and usually shows other signs of hemolysis.

So the reason Gilbert syndrome stands out is that it’s a frequent, benign contributor to mild unconjugated hyperbilirubinemia in the general population, making it the most common cause.