{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:20Z","timestamp":1760060720151,"version":"build-2065373602"},"reference-count":20,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shin Poong Pharmaceutical Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Ulipristal acetate (UPA) is a selective progesterone receptor modulator approved for the treatment of uterine fibroids, but concerns have arisen regarding its potential for severe hepatotoxicity, particularly following regulatory warnings in Europe and Korea. The real-world risk of UPA-induced liver injury in Korean women remains largely unknown. To evaluate the hepatic safety of UPA among Korean women with uterine fibroids using large-scale, population-based healthcare claims and health screening data. Methods: A retrospective, propensity score-matched cohort study was conducted using the Korean National Health Insurance Service database. Women diagnosed with uterine fibroids who received UPA between 2013 and 2016 (n = 12,166) were compared to matched controls (n = 36,498) who did not receive UPA. Primary outcomes included changes in liver enzymes (AST, ALT, \u03b3-GTP) and Fatty Liver Index (FLI) before and after UPA use. Results: UPA users showed small but statistically significant increases in ALT, \u03b3-GTP, and FLI compared to pre-treatment values, though all values remained within normal reference ranges. Odds of elevated FLI (\u226560) and \u03b3-GTP (\u226540 IU\/L) were modestly increased in the UPA group, but no cases of severe hepatotoxicity or liver failure occurred. Conclusions: UPA use in Korean women was associated with mild, subclinical elevations in liver enzymes and fatty liver index, but not with clinically significant hepatotoxicity. These findings support vigilant hepatic monitoring during UPA therapy, while contextualizing its risk as low in this population.<\/jats:p>","DOI":"10.3390\/jcm14186496","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T07:33:02Z","timestamp":1758007982000},"page":"6496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Hepatic Safety of Ulipristal Acetate in Korean Women with Uterine Fibroids: A Real-World Study Using Biochemical Markers"],"prefix":"10.3390","volume":"14","author":[{"given":"Jung Yoon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong","family":"Namkung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0577-1253","authenticated-orcid":false,"given":"Yong Han","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Soonchunhyang University Cheonan Hospital, Cheonan-si 31151, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8186-6230","authenticated-orcid":false,"given":"Younjee","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0140-6736(00)03622-9","article-title":"Uterine fibroids","volume":"357","author":"Stewart","year":"2001","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"(2021). Management of Symptomatic Uterine Leiomyomas: ACOG Practice Bulletin, Number 228. Obstet. Gynecol., 137, e100\u2013e115.","DOI":"10.1097\/AOG.0000000000004401"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1056\/NEJMoa1103182","article-title":"Ulipristal acetate versus placebo for fibroid treatment before surgery","volume":"366","author":"Donnez","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.fertnstert.2014.10.038","article-title":"Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids","volume":"103","author":"Donnez","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_5","unstructured":"(2025, August 08). European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/news\/esmya-new-measures-minimise-risk-rare-serious-liver-injury-0?utm_source=chatgpt.com."},{"key":"ref_6","unstructured":"(2025, March 23). Korean Ministry of Food and Drug Safety, Available online: https:\/\/nedrug.mfds.go.kr\/pbp\/CCBAC01\/getItem?safeLetterNo=249."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The Fatty Liver Index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000519752","article-title":"Marked Increase of Gamma-Glutamyltransferase as an Indicator of Drug-Induced Liver Injury in Patients without Conventional Diagnostic Criteria of Acute Liver Injury","volume":"38","author":"Weber","year":"2022","journal-title":"Visc. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"pyv126","DOI":"10.1093\/ijnp\/pyv126","article-title":"Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program","volume":"19","author":"Friedrich","year":"2015","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Carli, F., Sabatini, S., Gaggini, M., Sironi, A.M., Bedogni, G., and Gastaldelli, A. (2023). Fatty Liver Index (FLI) Identifies Not Only Individuals with Liver Steatosis but Also at High Cardiometabolic Risk. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914651"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Biciusca, T., Stan, S.I., Balteanu, M.A., Cioboata, R., Ghenea, A.E., Danoiu, S., Bumbea, A.M., and Biciusca, V. (2023). The Role of the Fatty Liver Index (FLI) in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review. Diagnostics, 13.","DOI":"10.3390\/diagnostics13213316"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.15403\/jgld-3404","article-title":"Fatty Liver Index as a Simple and Useful Predictor for 10-year Cardiovascular Disease Risks Determined by Framingham Risk Score in the General Korean Population","volume":"30","author":"Chung","year":"2021","journal-title":"J. Gastrointest. Liver Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1080\/14740338.2018.1550070","article-title":"Liver safety parameters of ulipristal acetate for the treatment of uterine fibroids: A comprehensive review of the clinical development program","volume":"17","author":"Donnez","year":"2018","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1007\/s40264-020-00975-8","article-title":"Liver Injury with Ulipristal Acetate: Exploring the Underlying Pharmacological Basis","volume":"43","author":"Gatti","year":"2020","journal-title":"Drug Saf."},{"key":"ref_15","first-page":"CD000547","article-title":"Preoperative medical therapy before surgery for uterine fibroids","volume":"4","author":"Puscasiu","year":"2025","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mici\u0107, J., Macura, M., Andji\u0107, M., Ivanovi\u0107, K., Dotli\u0107, J., Mici\u0107, D.D., Arsenijevi\u0107, V., Stojni\u0107, J., Bila, J., and Babi\u0107, S. (2024). Currently Available Treatment Modalities for Uterine Fibroids. Medicina, 60.","DOI":"10.3390\/medicina60060868"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"123345","DOI":"10.1016\/j.lfs.2024.123345","article-title":"Progesterone signaling in uterine fibroids: Molecular mechanisms and therapeutic opportunities","volume":"362","author":"Ploumaki","year":"2025","journal-title":"Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.fertnstert.2024.02.046","article-title":"Functional evidence for two distinct mechanisms of action of progesterone and selective progesterone receptor modulator on uterine leiomyomas","volume":"122","author":"Milewska","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2147\/TCRM.S273358","article-title":"Hepatic Safety Considerations in the Use of Ulipristal Acetate for Symptomatic Uterine Fibroids","volume":"21","author":"Semmler","year":"2025","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1210\/clinem\/dgab081","article-title":"Use of ulipristal acetate and risk of liver disease: A nationwide cohort study","volume":"106","author":"Yoon","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/18\/6496\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:45:56Z","timestamp":1760035556000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/18\/6496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":20,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["jcm14186496"],"URL":"https:\/\/doi.org\/10.3390\/jcm14186496","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,9,15]]}}}