{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:30:43Z","timestamp":1784662243320,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Drug Saf. Regul."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>olaparib is a Poly ADP-Ribose Polymerase inhibitor approved for the treatment of BRCA-mutated tumors, and has been associated with hepatotoxicity, as highlighted by the Pharmacovigilance Risk Assessment Committee.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives and methods<\/jats:title>\n                    <jats:p>to describe Drug-Induced Liver Injury (DILI) cases related to olaparib stratifying them by liver damage origin in \u201ccholestatic\u201d, \u201ccytolytic\u201d, \u201cmixed\u201d, \u201cliver related investigation\u201d and \u201cnot specified\u201d cases, by analyzing data from EudraVigilance (EV) database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>344 Individual Case Safety Reports (ICSRs) reporting olaparib-induced liver injury cases were retrieved from the EV. They referred more frequently to female patients belonging to the age group 18\u201364\u00a0years. The majority of ICSRs (66.0%) reported serious Adverse events (AEs), classified as \u201cOther Medically Important Condition\u201d, while 23 ICSRs reported fatal AEs. Among the 344 DILI cases, 19.5% were classified as \u201ccytolytic\u201d, 3.5% as \u201ccholestatic\u201d and 1.5% as \u201cmixed\u201d origin. Most DILI cases were temporally associated with \u201cliver-related investigations\u201d (39.8%) and 15.1% were classified as \u201cnot specified\u201d. A further 20.6% of cases involved PTs related to liver neoplasms (benign or malignant).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Further pharmacovigilance studies are needed to evaluate the hepatic safety profile of olaparib. Investigating the pathophysiological mechanisms underlying olaparib-induced liver injury could offer clinicians valuable insights for its prevention and management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fdsfr.2025.1736759","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:41:43Z","timestamp":1767940903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatobiliary adverse drug reactions during treatment with olaparib: an analysis of data from the EudraVigilance reporting system"],"prefix":"10.3389","volume":"5","author":[{"given":"Elena-Mirabela","family":"Veli\u015fcu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Cagnotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giuseppa","family":"Sullo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Anatriello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Salvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Scavone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/clpt.2011.58","article-title":"Case definition and phenotype standardization in drug-induced liver injury","volume":"89","author":"Aithal","year":"2011","journal-title":"Clin. Pharmacology Therapeutics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e00735","DOI":"10.14309\/crj.0000000000000735","article-title":"Olaparib-induced immune-mediated liver injury","volume":"9","author":"Alshelleh","year":"2022","journal-title":"ACG Case Reports Journal"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1016\/s1470-2045(21)00531-3","article-title":"Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1\/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"22","author":"Banerjee","year":"2021","journal-title":"Lancet Oncol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ejim.2021.10.035","article-title":"Drug-induced liver injury: pathogenesis, epidemiology, clinical features, and practical management","volume":"97","author":"Bj\u00f6rnsson","year":"2022","journal-title":"Eur. Journal Internal Medicine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/978-3-319-91442-8_15","article-title":"Olaparib","volume":"211","author":"Bochum","year":"2018","journal-title":"Recent Results Cancer Research."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3888","DOI":"10.3390\/cancers14163888","article-title":"BRCA mutations in ovarian and prostate cancer: bench to bedside","volume":"14","author":"Boussios","year":"2022","journal-title":"Cancers"},{"key":"B7","doi-asserted-by":"publisher","first-page":"145","DOI":"10.2165\/00002018-200326030-00002","article-title":"Methods and pitfalls in searching drug safety databases utilising the medical dictionary for regulatory activities (MedDRA)","volume":"26","author":"Brown","year":"2003","journal-title":"Drug Saf."},{"key":"B8","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1200\/JCO.22.01549","article-title":"Overall survival with maintenance olaparib at a 7-Year Follow-Up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1\/GOG 3004 trial","volume":"41","author":"DiSilvestro","year":"2023","journal-title":"J. Clinical Oncology"},{"key":"B9","first-page":"937","article-title":"Diagnosis and management of ovarian cancer","volume":"93","author":"Doubeni","year":"2016","journal-title":"Am. Family Physician"},{"key":"B10","unstructured":"ICH topic E 2 A clinical safety data management: definitions and standards for expedited reporting\n          \n          \n          2023"},{"key":"B11","unstructured":"Serious adverse reaction\n          \n          \n          2024"},{"key":"B12","unstructured":"PRAC recommendations on signals\n          \n          \n          2025"},{"key":"B13","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1200\/JCO.23.01868","article-title":"FDA approval summary: olaparib in combination with abiraterone for treatment of patients with BRCA-mutated metastatic castration-resistant prostate cancer","volume":"42","author":"Fallah","year":"2024","journal-title":"J. Clinical Oncology"},{"key":"B14","unstructured":"FDA approves olaparib tablets for maintenance treatment in ovarian cancer"},{"key":"B15","unstructured":"FDA approves olaparib for germline BRCA-Mutated metastatic breast cancer"},{"key":"B16","unstructured":"FDA approves olaparib for gBRCAm metastatic pancreatic adenocarcinoma"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3381","DOI":"10.1007\/s00204-020-02885-1","article-title":"Drug induced liver injury: an update","volume":"94","author":"Garcia-Cortes","year":"2020","journal-title":"Arch. Toxicol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1056\/NEJMoa1903387","article-title":"Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer","volume":"381","author":"Golan","year":"2019","journal-title":"N. Engl. Journal Medicine"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.2147\/CMAR.S169558","article-title":"The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials","volume":"10","author":"Guo","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4257","DOI":"10.1158\/1078-0432.CCR-15-0887","article-title":"FDA approval summary: olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy","volume":"21","author":"Kim","year":"2015","journal-title":"Clin. Cancer Research An Official Journal Am. Assoc. Cancer Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"E310","DOI":"10.1503\/cmaj.202026","article-title":"Drug-induced liver injury","volume":"193","author":"Kumachev","year":"2021","journal-title":"CMAJ"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3039","DOI":"10.1007\/s00204-017-2024-8","article-title":"A review of drug-induced liver injury databases","volume":"91","author":"Luo","year":"2017","journal-title":"Archives Toxicol."},{"key":"B23","unstructured":"Introductory guide for standardised MedDRA queries (SMQs)\n          \n          \n          2025"},{"key":"B24","doi-asserted-by":"publisher","first-page":"617","DOI":"10.2165\/00002018-200730070-00009","article-title":"Standardised MedDRA queries: their role in signal detection","volume":"30","author":"Mozzicato","year":"2007","journal-title":"Drug Saf."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.3390\/ph16111611","article-title":"Skin toxicities associated with botulin toxin injection for aesthetic procedures: data from the European spontaneous reporting system","volume":"16","author":"Nicoletti","year":"2023","journal-title":"Pharm. Basel, Switz."},{"key":"B26","unstructured":"Nih.gov; national institute of diabetes and digestive and kidney diseases\n          \n          \n          2017"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bpobgyn.2021.11.007","article-title":"Breast cancer screening in average and high-risk women. Best practice & research","volume":"83","author":"Rahman","year":"2022","journal-title":"Clin. Obstetrics & Gynaecology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1056\/NEJMoa1706450","article-title":"Olaparib for metastatic breast cancer in patients with a germline BRCA mutation","volume":"377","author":"Robson","year":"2017","journal-title":"N. Engl. Journal Medicine"},{"key":"B29","unstructured":"Nih.gov; national institute of diabetes and digestive and kidney diseases\n          \n          \n          2017"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1007\/s00228-018-2480-y","article-title":"Sex differences in spontaneous reports on adverse drug events for common antihypertensive drugs","volume":"74","author":"Rydberg","year":"2018","journal-title":"Eur. Journal Clinical Pharmacology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA adverse event reporting system","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s40801-019-00174-7","article-title":"Severe cutaneous adverse drug reactions associated with allopurinol: an analysis of spontaneous reporting system in southern Italy","volume":"7","author":"Scavone","year":"2020","journal-title":"Drugs - Real World Outcomes"},{"key":"B33","doi-asserted-by":"publisher","first-page":"211","DOI":"10.4236\/ojgas.2021.1111022","article-title":"Etiologies of liver cytolysis in the service of hepato-gastroenterology of the gabriel toure university hospital","volume":"11","author":"Sow","year":"2021","journal-title":"Open J. Gastroenterology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/978-3-642-30726-3_5","article-title":"Sex differences in drug effects: interaction with sex hormones in adult life","author":"Spoletini","year":"2012","journal-title":"Handb. Experimental Pharmacology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.annonc.2020.10.470","article-title":"A meta-analysis of reversion mutations in BRCA genes identifies signatures of DNA end-joining repair mechanisms driving therapy resistance","volume":"32","author":"Tobalina","year":"2021","journal-title":"Ann. Oncology Official Journal Eur. Soc. Med. Oncol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1002\/hep.30119","article-title":"A case of immune-mediated liver injury induced by olaparib","volume":"68","author":"Tufoni","year":"2018","journal-title":"Hepatol. Baltim. Md"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.3390\/ph16081071","article-title":"Hepatobiliary adverse reactions during treatment with cladribine: analysis of data from the European spontaneous reporting system","volume":"16","author":"Veli\u015fcu","year":"2023","journal-title":"Pharmaceuticals"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bpobgyn.2016.08.006","article-title":"Epidemiology of epithelial ovarian cancer. Best practice & research","volume":"41","author":"Webb","year":"2017","journal-title":"Clin. Obstetrics & Gynaecology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12943-021-01315-9","article-title":"PARP inhibitor olaparib overcomes sorafenib resistance through reshaping the pluripotent transcriptome in hepatocellular carcinoma","volume":"20","author":"Yang","year":"2021","journal-title":"Mol. Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"101439","DOI":"10.1016\/j.gore.2024.101439","article-title":"Challenges in PARP inhibitor therapy: a case of olaparib-induced liver injury and successful rechallenge with niraparib","volume":"54","author":"Zhu","year":"2024","journal-title":"Gynecol. Oncol. Rep."}],"container-title":["Frontiers in Drug Safety and Regulation"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdsfr.2025.1736759\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:41:44Z","timestamp":1767940904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdsfr.2025.1736759\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":40,"alternative-id":["10.3389\/fdsfr.2025.1736759"],"URL":"https:\/\/doi.org\/10.3389\/fdsfr.2025.1736759","relation":{},"ISSN":["2674-0869"],"issn-type":[{"value":"2674-0869","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]},"article-number":"1736759"}}