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Our study investigated the association between PPI use and hepatocellular carcinoma (HCC) recurrence following curative surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively enrolled 6037 patients with HCC who underwent hepatectomy. Patients were divided into four groups according to their PPI usage. (non\u2010users: &lt;\u00a028 cumulative defined daily dose [cDDD]; short\u2010term users: 28\u201389 cDDD; mid\u2010term users: 90\u2013179 cDDD, and long\u2010term users: \u2265\u00a0180 cDDD, respectively). Recurrence\u2010free survival (RFS) and overall survival (OS) were analyzed using Kaplan\u2013Meier method and Cox proportional hazard models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 6037 HCC patients, 2043 (33.84%) were PPI users. PPI users demonstrated better median RFS (3.10\u00a0years, interquartile range [IQR] 1.49\u20135.01) compared with non\u2010users (2.73\u00a0years, IQR 1.20\u20134.74; with an adjusted hazard ratio [aHR] of 0.57, 95% confidence interval [CI] 0.44\u20130.74, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). When considering the cumulative dosage of PPI, only long\u2010term PPI users had significant lower risk of HCC recurrence than non\u2010PPI group (adj\u2010HR: 0.50; 95% CI: 0.35\u20130.70; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Moreover, the impact of long\u2010term PPIs use on improving RFS was significant in most of the subgroup analysis, except in patients with advanced tumor stages, with non\u2010cirrhosis, or with a history of chronic kidney disease. However, there were no significant differences in median OS between PPI users and non\u2010users (4.23\u00a0years, IQR 2.73\u20135.86 <jats:italic>vs<\/jats:italic> 4.04\u00a0years, IQR 2.51\u20135.82, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.369).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Long\u2010term PPI use (\u2265\u00a0180 cDDD) may be associated with a better RFS in HCC patients after hepatectomy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.16640","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T13:05:17Z","timestamp":1718197517000},"page":"2077-2087","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The association between proton\u2010pump inhibitor use and recurrence of hepatocellular carcinoma after hepatectomy"],"prefix":"10.1111","volume":"39","author":[{"given":"Chun\u2010Ting","family":"Ho","sequence":"first","affiliation":[{"name":"Department of General Medicine, Department of Medicine Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"School of Medicine, College of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Chu","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Department of Medicine Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8115-3011","authenticated-orcid":false,"given":"Elise Chia\u2010Hui","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Health Service Administration, College of Public Health China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Yu","family":"Kao","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine Taipei Medical University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Chang","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-5425","authenticated-orcid":false,"given":"Yi\u2010Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Institute of Clinical Medicine, College of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2202-521X","authenticated-orcid":false,"given":"Teh\u2010Ia","family":"Huo","sequence":"additional","affiliation":[{"name":"Division of Basic Research, Department of Medical Research Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4886-0718","authenticated-orcid":false,"given":"Ming\u2010Chih","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Taipei Veterans General Hospital  Taipei 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