{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T02:03:50Z","timestamp":1781316230890,"version":"3.54.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation\u2010wide population\u2010based cohort in Sweden.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Using nation\u2010wide registries, we identified all adults who received maintenance PPIs (\u2265180\u00a0days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow\u2010up of 5.3\u00a0years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37\u20101.81), 1.77 (95% CI, 1.56\u20102.00), and 1.88 (95% CI, 1.57\u20102.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17\u20101.57) and 1.47 (95% CI, 1.19\u20101.80) for extra\u2010 and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with \u22655\u00a0years of PPIs use, ruling out confounding by indication.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\u00a0In this study, long\u2010term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31914","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T03:36:36Z","timestamp":1621568196000},"page":"2021-2031","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":25,"title":["Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population\u2010Based Cohort Study"],"prefix":"10.1097","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6662-7813","authenticated-orcid":false,"given":"Habiba","family":"Kamal","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases,Karolinska University Hospital,Stockholm,Sweden"},{"name":"Department of Medicine Huddinge,Karolinska Institutet,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Sadr\u2010Azodi","sequence":"additional","affiliation":[{"name":"Unit of Surgery,Department of Clinical Sciences, Intervention and Technology,Karolinska Institutet,Stockholm,Sweden"},{"name":"Department of Surgery,Capio Saint G\u00f6ran Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Engstrand","sequence":"additional","affiliation":[{"name":"Centre for Translational Microbiome Research,Department of Microbiology, Tumor and Cell Biology,Karolinska Institutet,Stockholm,Sweden"},{"name":"Global Health Institute,Antwerp University,Antwerp,Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nele","family":"Brusselaers","sequence":"additional","affiliation":[{"name":"Centre for Translational Microbiome Research,Department of Microbiology, Tumor and Cell Biology,Karolinska Institutet,Stockholm,Sweden"},{"name":"Global Health Institute,Antwerp University,Antwerp,Belgium"},{"name":"Department of Head and Skin,Ghent University Hospital,Ghent,Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"hep31914-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","article-title":"Expert consensus document: cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma 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