Drug-Induced Liver Injury Assessment and Management

Introduction to DILI Assessment Tools

Hy's Law identifies drugs with potential to cause severe or fatal hepatocellular liver injury, defined by ALT/AST ≥3× upper limit of normal (ULN) with concurrent total bilirubin ≥2× ULN, absence of cholestasis, and no competing etiology, as recommended by the American Association for the Study of Liver Diseases 1, 2
The European Association for the Study of the Liver suggests that Hy's Law predicts >10% risk of severe or fatal DILI in non-oncology populations 2

For hepatocellular injury with ALT >3× ULN and total bilirubin ≥2× ULN, the American College of Gastroenterology recommends immediately discontinuing the suspected drug and referring urgently to a liver transplant center 2
The National Institute of Diabetes and Digestive and Kidney Diseases advises measuring ALT, AST, alkaline phosphatase, total and direct bilirubin, and INR immediately, and calculating R value to determine injury pattern 3, 4
The American Association for the Study of Liver Diseases recommends excluding alternative causes urgently, such as viral hepatitis, autoimmune hepatitis, ischemic hepatopathy, and biliary obstruction 4

The European Association for the Study of the Liver suggests permanently discontinuing the drug if ALT >20× ULN regardless of bilirubin, or if ALT >3× ULN with total bilirubin ≥2× ULN, for patients with normal baseline liver tests 2
For patients with abnormal baseline ALT, the American College of Gastroenterology recommends withholding the drug if ALT >6× ULN, and permanently discontinuing if ALT >4× ULN with bilirubin ≥2× ULN 2

The American Association for the Study of Liver Diseases recommends repeating liver tests within 2-5 days for hepatocellular injury patterns, and within 7-10 days for cholestatic injury patterns 3, 5
The National Institute of Diabetes and Digestive and Kidney Diseases advises monitoring every 1-2 months for at least 6 months, then every 3 months if stable, after normalization of liver tests 5

The American College of Gastroenterology notes that management is primarily supportive, and there is no specific antidote for most DILI cases, except for N-acetylcysteine which is indicated only for acetaminophen toxicity 4
The European Association for the Study of the Liver emphasizes the importance of early referral to a transplant center, especially for non-acetaminophen DILI which has a worse prognosis 4