{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:02:04Z","timestamp":1792450924343,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Gamma-glutamyl transferase (GGT) has been associated with increased risks of multiple cancers and mortality. Because GGT is also a marker of hepatobiliary injury, metabolic dysfunction, and alcohol exposure, this study evaluated associations between persistently elevated GGT and hepatobiliary and pancreatic outcomes. Materials and Methods: This retrospective cohort study used TriNetX data from the US Collaborative Network to compare adults aged 40 years or older with persistently elevated GGT against those with normal GGT using a 65 U\/L threshold on two occasions 6\u201312 months apart. Outcomes were assessed from 180 to 1095 days after the index event. Following 1:1 propensity score matching, 14,590 patients per cohort were analyzed. Cox proportional hazards analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Elevated GGT was associated with increased hazards of cholangiocarcinoma (HR 3.715, 95% CI 1.899\u20137.268), hepatocellular carcinoma (HR 2.260, 95% CI 1.677\u20133.045), acute pancreatitis (HR 3.359, 95% CI 2.284\u20134.941), chronic pancreatitis (HR 3.086, 95% CI 1.975\u20134.821), pancreatic cysts (HR 2.160, 95% CI 1.493\u20133.127), hospitalization (HR 1.363, 95% CI 1.236\u20131.503), and all-cause mortality (HR 2.250, 95% CI 2.051\u20132.467). No statistically significant association was observed with pancreatic cancer (HR 1.591, 95% CI 0.766\u20133.303; log-rank p = 0.209). Mean follow-up after matching was 799.722 \u00b1 391.071 days in the elevated GGT cohort and 844.685 \u00b1 374.676 days in controls. Conclusions: Persistent GGT elevation was associated with hepatobiliary malignancies, pancreatic inflammatory diseases, pancreatic cysts, hospitalization, and all-cause mortality, but not pancreatic cancer. These results suggest that persistent GGT elevation may be a non-specific clinical marker of underlying hepatobiliary and metabolic risk.<\/jats:p>","DOI":"10.3390\/cancers18101512","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:14:16Z","timestamp":1778530456000},"page":"1512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Persistently Elevated Gamma-Glutamyl Transferase and Hepatobiliary Malignancies: A Real-World Cohort Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-2569","authenticated-orcid":false,"given":"Arkadeep","family":"Dhali","sequence":"first","affiliation":[{"name":"Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AU, UK"},{"name":"School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-9039","authenticated-orcid":false,"given":"Dushyant Singh","family":"Dahiya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Rafae","family":"Faisal","sequence":"additional","affiliation":[{"name":"Department of General Medicine, CMH Multan Institute of Medical Sciences, Multan 60010, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0735-6202","authenticated-orcid":false,"given":"Asad","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of General Medicine, CMH Multan Institute of Medical Sciences, Multan 60010, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2402-8890","authenticated-orcid":false,"given":"Fayaz","family":"Khan","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9357-0448","authenticated-orcid":false,"given":"Jyotirmoy","family":"Biswas","sequence":"additional","affiliation":[{"name":"Barasat Government Medical College and Hospital, Kolkata 700124, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7979-2834","authenticated-orcid":false,"given":"Hareesha Rishab","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"University Hospitals of North Midlands NHS Trust, Stoke-on-Trent ST4 6QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saikat","family":"Mandal","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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