Innovative Liver Organoid Platform Enhances Personalized Drug Safety

Researchers at Cincinnati Children's Hospital Medical Center, in collaboration with Roche, have developed a human liver organoid microarray platform that accurately models immune-mediated drug-induced liver injury (iDILI). This innovative system, detailed in a study published online on September 26, 2025, in Advanced Science, combines liver organoids derived from patient-induced pluripotent stem cells (iPSCs) with the patient's own CD8⁺ T cells. The platform successfully replicated liver damage caused by the antibiotic flucloxacillin in individuals carrying the HLA-B*57:01 risk gene, demonstrating its potential for personalized drug safety testing.

Drug-induced liver injury (DILI) is a significant cause of acute liver failure and poses challenges in drug development and patient safety. Idiosyncratic DILI (iDILI) is particularly concerning due to its unpredictable nature and potential severity. Certain genetic factors, notably specific human leukocyte antigen (HLA) alleles, have been linked to an increased risk of iDILI. The HLA-B57:01 allele has been associated with adverse reactions to drugs such as abacavir and flucloxacillin. For instance, individuals carrying the HLA-B57:01 allele have an approximately 80-fold increased risk of developing liver injury when treated with flucloxacillin.

The development of this organoid platform represents a significant advancement in personalized medicine. By accurately modeling immune-mediated DILI, the system allows for the assessment of drug safety on an individual basis, potentially reducing the incidence of adverse drug reactions. This approach could lead to more tailored treatment plans, minimizing risks for patients with specific genetic predispositions.

The collaboration between Cincinnati Children's Hospital Medical Center and Roche has led to a groundbreaking tool in the form of a human liver organoid microarray platform. This development holds promise for enhancing drug safety and efficacy, particularly for individuals with genetic susceptibilities to certain medications. As personalized medicine continues to evolve, such innovations are crucial in tailoring healthcare to individual genetic profiles, ultimately improving patient outcomes.