TABLE 1.
DILI classification8 | ||
---|---|---|
Intrinsic | Dose dependent and predictable (e.g. paracetamol) | |
Idiosyncratic | Unexpected hepatotoxic reaction in a small population exposed to the agent |
Hy's law, based on 3 components9 | Definition | |
---|---|---|
1 | Hepatocellular injury | Elevation of ≥3 times the ULN of: ALT and AST |
2 | Elevation of serum TB without findings of cholestasis | Elevation of serum TB ≥ 2 times the ULN |
3 | No other cause found for increased aminotransferases | Possible other causes: Viral hepatitis; alcohol abuses |
European Medicine Agency cut‐off values: Combination of component 1 and 2.10 |
‐ ALT/AST ≥3 times ULN ‐ TB ≥2 times the ULN |
DILI‐network grading scales8 | ||
---|---|---|
1 | Mild |
‐ elevated ALT and/or AST ‐ but TB below Hy's law and INR < 1.5 |
2 | Moderate |
‐ all LFTs meeting Hy's law ‐ or INR ≥ 1.5 |
3 | Moderate–severe |
‐ LFTs meeting Hy's law ‐ hospitalization or ongoing hospitalization prolonged due to DILI |
4 | Severe* |
LFTs meeting Hy's law and at least 1 of the following criteria: ‐ hepatic failure (INR > 1.5, ascites or encephalopathy) ‐ other organ failure due to DILI |
5 | Fatal* | Death or liver transplantation due to DILI |
In most fatal cases, ALT and AST were 8–100× ULN9
Hy's law criteria are thought to indicate severe hepatocellular injury that is associated with at least 10% chance of severe liver failure and/or need for liver transplantation.53, 54
The DILI Network combines death and the need for liver transplantation in the fatal definition, which are identified separately in this paper as severe (in need of liver transplantation) and fatal (death).
ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; LFT, liver function tests; TB, total bilirubin; ULN, upper limit of normal