Efficacy and safety of glucocorticoids for acute drug-induced liver injury with hyperbilirubinemia: protocol of a multicenter randomized controlled trial.

Background: Drug-induced liver injury (DILI) can lead to potentially fatal complications, such as acute liver failure and even death. In clinical practice, glucocorticoids have been considered in some cases of DILI, especially those with hyperbilirubinemia. However, the available evidence remains controversial and its quality is also very limited. Objectives: To explore the efficacy and safety of glucocorticoids in patients with acute DILI and hyperbilirubinemia. Design: An open-label, multicenter, randomized controlled trial (RCT). Methods and analysis: Overall, 232 patients with acute DILI with hyperbilirubinemia will be enrolled, and then, randomly assigned at a ratio of 1:1 to the conventional treatment alone or combined with glucocorticoids groups. The primary endpoint is the improvement of DILI, which is defined as total bilirubin level decreased by 50% after treatment, at the 2nd week. Secondary endpoints include the improvement of DILI at the 4th week and rates of progressive liver injury, liver failure, liver transplantation, survival, and adverse events. As for exploratory endpoints, we will also identify the beneficial population and assess the changes of inflammatory factors following glucocorticoids treatment. Ethics: The study has been approved by the Medical Ethical Committee of the General Hospital of Northern Theater Command (ethical approval number Y2024-226) as well as 11 other participating centers. Discussion: This RCT will provide solid evidence to clarify the benefits of glucocorticoids in patients with acute DILI and hyperbilirubinemia. Trial registration: ClinicalTrials.gov identifier: NCT06922669.