Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset

Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%-6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.