Features and Outcomes of 280 Patients With Idiosyncratic Drug-Induced Liver Injury: The REFHEPS Prospective Study

Area of Science:

• Hepatology
• Pharmacovigilance
• Internal Medicine

Background:

• The Réseau d'Etude Francophone de l'Hépatotoxicité des Produits de Santé (REFHEPS) is a joint French-Belgian network established in October 2021 to gather drug-induced liver injury (DILI) data.
• This study analyzes DILI cases prospectively collected by REFHEPS from January 2022 to June 2024, detailing clinical characteristics, outcomes, histology, and causative agents.

Purpose of the Study:

• To characterize drug-induced liver injury (DILI) cases within the REFHEPS network.
• To identify demographic, clinical, and etiological patterns of DILI, with a focus on idiosyncratic cases.
• To compare current DILI trends with historical data, particularly regarding the impact of novel therapeutics.

Main Methods:

• Prospective data collection of DILI cases within the REFHEPS network.
• Application of Council for International Organizations of Medical Sciences (CIOMS) and Drug-Induced Liver Injury Network (DILIN) criteria for case definition and severity assessment.
• Utilized the Roussel-Uclaf Causality Assessment Method (RUCAM) scale for causality assessment.

Main Results:

• A total of 322 DILI cases were analyzed, with 280 classified as idiosyncratic.
• Significant sex-related differences were observed: females were younger and more prone to hepatocellular DILI.
• Anticancer drugs, particularly immune checkpoint inhibitors, were identified as the primary cause of DILI in 68.9% of cases.

Conclusions:

• The REFHEPS registry has successfully collected a substantial number of DILI cases, revealing demographic variations.
• Findings confirm previously reported sex and age-related differences in DILI.
• A notable shift in DILI etiology is evident, with anticancer drugs and immune checkpoint inhibitors emerging as major contributors, highlighting new safety concerns with innovative therapies.