Photo Credit: iStock.com/EvgeniyShkolenko

Analysis of DILIN data revealed that initial R values best predicted Hy’s Law outcomes.

A study published in June 2025 issue of American Journal of Gastroenterology stated that Hy’s Law was associated with hepatocellular (HC) drug-induced liver injury (DILI) with jaundice to high mortality despite lacking defined timing of liver tests and clear classification criteria.  

Researchers determined the validity of Hy’s Law within the prospective DILI Network (DILIN) cohort.  

They analyzed drugs with ≥10 confirmed cases of DILI with jaundice and 4 versions of Hy’s Law were applied: R ≥ 5 using either initial or peak alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and the Food and Drug Administration criteria of alanine aminotransferase or aspartate aminotransferase ≥ 3× upper limit of normal with alkaline phosphatase ≤ 2× upper limit of normal using either initial or peak values. Mortality was described as death or liver transplant  attributed to DILI.  

The results showed that using initial R values, mortality was 11.1% for HC injury and 2.0% for cholestatic or mixed (C/M) injury (P < 0.001). Based on peak R values, mortality was 10.3% for HC and 1.6% for C/M (P < 0.001). Using the Food and Drug Administration definition, mortality with initial values was 7.9% for HC and 3.9% for C/M (P = 0.04), and peak values were 7.9% for HC and 3.0% for C/M (P = 0.01). Drugs frequently linked to HC injury showed mortality ≥ 10%, while those typically causing C/M injury had rates < 10%. Some drugs occasionally causing HC injury with jaundice had low mortality.  

Investigators concluded that initial R values most accurately identified Hy’s Law cases, though some HC injuries with jaundice had mortality rates below 10%, indicating a need to refine the criteria. 

Source: journals.lww.com/ajg/abstract/2025/06000/refinement_of_hy_law_using_the_drug_induced_liver.21.aspx