Management of Mildly Elevated Bilirubin in Patients on Statins

Rationale for Continuing Therapy

Drug-induced liver injury (DILI) requires ALT ≥3× ULN with bilirubin ≥2× ULN (Hy's Law criteria) to warrant drug interruption, as recommended by the American Gastroenterological Association 1, 2
Normal ALT and AST levels exclude hepatocellular injury, according to the American Gastroenterological Association 1, 2
Normal alkaline phosphatase levels exclude cholestatic injury, as stated by the American Gastroenterological Association 1, 3
A total bilirubin of 1.7 mg/dL is only mildly elevated and direct bilirubin of 0.4 mg/dL is only slightly elevated, as reported by the American Gastroenterological Association 1, 2

Recheck complete liver panel (ALT, AST, alkaline phosphatase, total and direct bilirubin) in 2-4 weeks, as recommended by the American Gastroenterological Association 1, 2
Interrupt rosuvastatin and ezetimibe ONLY if any of the following occur: ALT or AST ≥3× ULN with total bilirubin ≥2× ULN, ALT or AST ≥5× ULN regardless of bilirubin, development of liver-related symptoms, or alkaline phosphatase elevation suggesting cholestasis, according to the American Gastroenterological Association 1, 2, 4

Evaluate for non-drug causes of mild hyperbilirubinemia, such as Gilbert syndrome, hemolysis, or biliary obstruction, as recommended by the American College of Gastroenterology 4, 5
Gilbert syndrome is the most common cause of isolated unconjugated hyperbilirubinemia, affecting 3-7% of the population, and is benign, according to the American College of Gastroenterology 4

The cardiovascular benefit of continuing statin and ezetimibe therapy far outweighs the risk from this mild, isolated bilirubin elevation, as stated by the American College of Cardiology 6