Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia

Efficacy and Safety of Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia: A Multicenter Randomized Controlled Trial

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 patients with hyperbilirubinemia. However, the available evidence remains controversial and its quality is also very limited. Herein, a multicenter randomized controlled trial (RCT) has been designed to explore the efficacy and safety of glucocorticoids in patients with acute DILI and hyperbilirubinemia.

Overall, 232 patients with acute DILI with hyperbilirubinemia will be enrolled. They will be 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 after treatment on second week. Secondary endpoints include the improvement of DILI on fourth week, rates of progressive liver injury, liver failure, liver transplantation, survival, and adverse events. Exploratory endpoints will assess the beneficial population and changes of inflammatory factors following glucocorticoid treatment.

Inclusion Criteria:

• A definite diagnosis of acute DILI;
• 5×ULN ≤ TBIL level at baseline ≤ 20×ULN;
• Age 18-80 years old;
• Sign the informed consent form.

Exclusion Criteria:

• Other causes of liver injury, including viral hepatitis, cytomegalovirus infection, Epstein-Barr virus infection, Herpes virus infection, autoimmune liver disease, alcoholic liver disease, hypoxic/ischemic liver disease, Budd-Chiari syndrome, biliary tract disease, Wilson's disease, hemochromatosis, and α1-antitrypsin deficiency;
• Immune checkpoint inhibitors or gynura segetum induced DILI;
• Absolute contraindications to glucocorticoids, such as systemic mold infections or allergies;
• A history of glucocorticoid therapy within 3 months before enrollment;
• A history of diseases requiring glucocorticoid maintenance therapy, such as rheumatoid arthritis, systemic lupus erythematosus, systemic dermatomyositis, etc;
• A history of liver transplantation;
• Received artificial liver therapy before enrollment;
• Malignant tumor of the liver, bile duct, pancreas or liver metastasis
• Acute liver failure;
• Renal dysfunction, creatinine Cr≥133μmol/L;
• Neutrophil count <1,000,000,000/L;
• Active tuberculosis;
• Severe cardiopulmonary diseases;
• Recent surgery or trauma;
• Mental illness;
• Pregnancy or lactation;
• Participated in other clinical studies within 3 months before enrollment;
• Other conditions judged by the clinician to be inappropriate for study participation.