Drug‐induced liver injury (DILI) is the main cause of death and indication for liver transplantation (fatality). The role of DILI in these mortalities is poorly characterized, particularly when fatalities occur >26 weeks after DILI onset. Patients were analyzed in the US Drug‐Induced Liver Injury Network prospective study having a fatal outcome within 2 years of onset. Primary role were subcategorized as acute, chronic, acute‐on‐chronic, or acute cholestatic liver failure. Among 1,089 patients, 107 (9.8%) fatalities occurred within 2 years. DILI had a primary role in 68 (64%), a contributory role in 15 (14%), and no role in 22 (21%); 2 had insufficient data. Among primary role cases, 74% had acute, 13% chronic, 7% acute on chronic, and 6% acute cholestatic failure. For the 15 contributory role cases, common causes of death included sepsis, malignancy, and severe cutaneous reactions with multiorgan failure. For the 22 no role cases, malignancies accounted for most fatalities. Higher bilirubin, coagulopathy, leukocytosis, and thrombocytopenia were independently associated with DILI fatalities.

DILI leads directly or indirectly to fatality in 7.6% of cases; 40% of these had nonacute liver failure courses. New R ratio Hys law better identifies risk for death compared to the original Hys law.

Source: Hepatology 2017;66:1275‐1285.