Drug‐induced liver injury ( DILI ) ascribed to non‐steroidal anti‐inflammatory drugs ( NSAIDs ) in the USA —Update with genetic correlations
Year: 2024
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI. METHODS: In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort. RESULTS: Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac. CONCLUSIONS: Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses.
Source: Liver International
DOI: 10.1111/liv.15892
Institutions: Atrium Health Wake Forest Baptist, Wake Forest University, Indiana University Health, Indiana University Hospital, Indiana University School of Medicine, Icahn School of Medicine at Mount Sinai, Duke University, University of Michigan, Michigan Medicine, Duke Clinical Research Institute, Newcastle University, Nottingham University Hospitals NHS Trust, University of Nottingham, National Institute for Health and Care Research, NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham Biomedical Research Centre, Vanderbilt University, Vanderbilt University Medical Center, National Cancer Institute, Wake Forest University Health Sciences
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: bronze
Funders: Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G113261452, G1333635724, IU Clinical Center: Drug Induced Liver Injury Network, G151959291, Wake Forest Clinical and Translational Science Award, G2524710291, UT Southwestern: Clinical Site for the Drug-Induced Liver Injury Network, G3207883224, UNC Clinical and Translational Science Award, G38283659, Uppper Midwest Drug Hepatoxicity Consortium, "Drug Induced Liver Injury Network", Research Network for Drug-Induced Liver Disease, Diverse ancestry biobank to map biomedical traits and elucidate health disparitie, G4270823017, Michigan Institute for Clinical and Health Research (MICHR) (UL1), North and Central Texas Clinical and Translational Science Initiative (UL1), Indiana Clinical and Translational Science Institute (UL1), G506636106, Institutional Clinical and Translational Science Award, G5671986908, G7169620683, Michigan Hepatotoxicity Clinical Research Network Renewal, G8623707958, Mayo Clinic Center for Translational Science Activities, Herbal and Dietary Supplement Induced Liver Injury in the U.S., University of North Carolina Clinical Center for DILIN, USC-UCLA Drug-Induced Liver Injury (DILI) Clinical Center, Drug Induced Liver Injury Network Data Coordinating Center
OpenAlex ID: W4392551288