{"doi":"10.1111/liv.15892","title":"<scp>Drug‐induced</scp> liver injury (<scp>DILI</scp>) ascribed to non‐steroidal anti‐inflammatory drugs (<scp>NSAIDs</scp>) in the <scp>USA</scp>—Update with genetic correlations","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.","journal":"Liver International","year":2024,"id":428111,"datarank":0.4636642871836061,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.06780568774131718,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.06780568774131718,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":10,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8721,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00345930"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284722,"name":"Marwan Ghabril","orcid":"0000-0002-4784-3246","position":1,"is_corresponding":false},{"id":306531,"name":"Paola Nicoletti","orcid":null,"position":2,"is_corresponding":false},{"id":305211,"name":"Andrew Dellinger","orcid":"0000-0003-1650-4329","position":3,"is_corresponding":false},{"id":255436,"name":"Robert J. Fontana","orcid":"0000-0001-9161-5892","position":4,"is_corresponding":false},{"id":286135,"name":"Huiman X. Barnhart","orcid":"0000-0003-0988-3439","position":5,"is_corresponding":false},{"id":287345,"name":"Jiezhun Gu","orcid":null,"position":6,"is_corresponding":false},{"id":262350,"name":"Ann K. Daly","orcid":"0000-0002-7321-0629","position":7,"is_corresponding":false},{"id":305213,"name":"Guruprasad P. Aithal","orcid":"0000-0003-3924-4830","position":8,"is_corresponding":false},{"id":106289,"name":"Elizabeth J. Phillips","orcid":"0000-0002-7623-3383","position":9,"is_corresponding":false},{"id":225662,"name":"David E. Kleiner","orcid":"0000-0003-3442-4453","position":10,"is_corresponding":false},{"id":1229800,"name":"the US DILIN Investigators","orcid":null,"position":11,"is_corresponding":false},{"id":257153,"name":"Herbert L. Bonkovsky","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:58:57.592578Z","pmid":"38451034","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}