{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:39:49Z","timestamp":1793173189352,"version":"4.5.0"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JGH Open"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Ceftriaxone is widely used because of its broad antimicrobial spectrum and convenient dosing; however, high biliary excretion can lead to calcium\u2013ceftriaxone precipitation and gallstone\u2010like formations. Although exposure\u2010related risk factors have been described, the effect of hepatic fibrosis on ceftriaxone\u2010associated gallstone formations remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Aims<\/jats:title>\n To clarify the role of hepatic fibrosis in ceftriaxone\u2010related gallstone formation.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a retrospective study on adult patients who received intravenous ceftriaxone and underwent abdominal computed tomography at a tertiary hospital between October 2021 and July 2025. The primary outcome was newly detected gallstone formations during or after ceftriaxone therapy. Clinical variables, including treatment duration, cumulative dose, and fibrosis\u20104 index, were analyzed. Decision tree, Kaplan\u2013Meier, Cox proportional hazards, and receiver operating characteristic analyses were performed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among the 320 eligible patients, 98 (30.6%) developed newly detected gallstones. Patients with gallstones had longer treatment duration (10 vs. 6\u2009days,\n p<\/jats:italic>\n \u2009<\u20090.001), higher cumulative dose (22 vs. 10\u2009g,\n p<\/jats:italic>\n \u2009<\u20090.001), and higher fibrosis\u20104 scores (2.86 vs. 1.68,\n p<\/jats:italic>\n \u2009<\u20090.001). Decision tree analysis identified fibrosis\u20104 (cutoff: 2.56) as the primary stratifying variable modifying exposure\u2010related thresholds. Kaplan\u2013Meier analysis showed earlier gallstone development in patients with fibrosis\u20104\u2009\u2265\u20092.56. In multivariable Cox analysis, fibrosis\u20104\u2009\u2265\u20092.56 was independently associated with gallstone formation. The incorporation of fibrosis\u20104 improved model discrimination.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Elevated FIB\u20104 levels were independently associated with CRO\u2010related gallstone formation. The FIB\u20104 index may facilitate risk stratification during CRO therapy, although the observed association should not be interpreted as direct evidence of hepatic fibrosis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jgh3.70468","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:01:46Z","timestamp":1790409706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Fibrosis\u20104 Index Predicts Ceftriaxone\u2010Associated Gallstone Formation: Risk Stratification Using the Fibrosis\u20104 Index in a Clinical Cohort"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-9560","authenticated-orcid":false,"given":"Hideo","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Pharmacy Mie University Hospital Tsu Mie Japan"},{"name":"Department of Clinical Pharmaceutics, Division of Clinical Medical Science Mie University Graduate School of Medicine Tsu Mie Japan"},{"name":"Department of Clinical Infectious Diseases Aichi Medical University Hospital Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Hagihara","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology and Biomedical Sciences Aichi Medical University Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-6411","authenticated-orcid":false,"given":"Hiroshige","family":"Mikamo","sequence":"additional","affiliation":[{"name":"Department of Clinical Infectious Diseases Aichi Medical University Hospital Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-4410","authenticated-orcid":false,"given":"Takuya","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital Tsu Mie Japan"},{"name":"Department of Clinical Pharmaceutics, Division of Clinical Medical Science Mie University Graduate School of Medicine Tsu Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201908-1581ST"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11101291"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)90596-X"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2185\/jrm.2020-020"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000529522"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000440680"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-017-1493-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11080983"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21178"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.18-288"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2026.02.019"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.14309\/crj.2014.40"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3835825"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21496"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgf2.269"}],"container-title":["JGH 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