A recent study (VL Re et al. Clin Gastroenterol Hepatol 2015; 13: 2360-68) examined a retrospective cohort of 15,353 patients with presumed drug-induced liver injury (DILI) to formulate a more sensitive model for predicting liver failure.
The authors note that Hy’s Law has good specificity but poor sensitivity. In their population, Hy’s Law had a specificity of 0.92, negative predictive value of 0.99, sensitivity of 0.68, and a positive predictive value of 0.02.
- Hy’s law (named for Hyman Zimmerman): AST or ALT > 3 ULN and total bilirubin ≥2 ULN indicate serious hepatotoxicity with >10% mortality rate.
By incorporating data from platelet count and total bilirubin, the authors devised a Drug-Induced Liver Toxicity ALF Score which had a high sensitivity of 0.91 but a lower specificity of 0.76.
- DrILTox ALF Score = -0.00691292*platelet count + 0.19091500*total bilirubin (per mg/dL)
- Example: platelet count of 145 & total bilirubin of 3.0 yields a valued of -0.4296 which is above cut off of -1.081 indicating an increased risk of ALF.
Thus, low platelet counts and high bilirubins are strong predictors of acute liver failure (ALF) in the setting of DILI.
My take: Overall, the incidence of ALF due to drugs remains fairly low and determining that a specific drug induced liver injury remains problematic. This study shows that ALF can occur in those who do not meet Hy’s Law criteria and that more sensitive predictors are needed.
Related blog posts:
- Liver toxicity -where to look online | gutsandgrowth
- Advice on drug-induced liver injury (DILI) | gutsandgrowth
- Data on Drug-Induced Liver Injury | gutsandgrowth