{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T10:56:04Z","timestamp":1792839364346,"version":"4.5.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>In patients with NAFLD, those with type 2 diabetes mellitus (DM) have a high risk of progression to HCC. However, the determinants of HCC risk in these patients remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      We assembled a retrospective cohort of patients with NAFLD and DM diagnosed at 130 facilities in the Veterans Administration between 1\/1\/2004 and 12\/31\/2008. We followed patients from the date of NAFLD diagnosis to HCC, death, or 12\/31\/2018. We used landmark Cox proportional hazards models to determine the effects of anti\u2010DM medications (metformin, insulin, sulfonylureas) and glycemic control (percent of follow\u2010up time with hemoglobin A1c &lt; 7%) on the risk of HCC while adjusting for demographics and other metabolic traits (hypertension, obesity, dyslipidemia). We identified 85,963 patients with NAFLD and DM. In total, 524 patients developed HCC during a mean of 10.3 years of follow\u2010up. Most common treatments were metformin monotherapy (19.7%), metformin\u2010sulfonylureas (19.6%), insulin (9.3%), and sulfonylureas monotherapy (13.6%). Compared with no medication, metformin was associated with 20% lower risk of HCC (HR, 0.80; 95% CI, 0.93\u20130.98). Insulin had no effect on HCC risk (HR, 1.02; 95% CI, 0.85\u20131.22;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.85). Insulin in combination with other oral medications was associated with a 1.6 to 1.7\u2010fold higher risk of HCC. Adequate glycemic control was associated with a 31% lower risk of HCC (HR, 0.69; 95% CI, 0.62\u20130.78).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this large cohort of patients with NAFLD and DM, use of metformin was associated with a reduced risk of HCC, whereas use of combination therapy was associated with increased risk. Glycemic control can serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.32244","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T08:21:55Z","timestamp":1636964515000},"page":"1420-1428","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":106,"title":["Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease"],"prefix":"10.1097","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2953-4949","authenticated-orcid":false,"given":"Jennifer R.","family":"Kramer","sequence":"first","affiliation":[{"name":"Center for Innovations in Quality, Effectiveness and Safety (IQuESt),Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas,USA"},{"name":"Section of Health Services Research,Department of Medicine,Baylor College of Medicine,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8885-4507","authenticated-orcid":false,"given":"Yamini","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Center for Innovations in Quality, Effectiveness and Safety (IQuESt),Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas,USA"},{"name":"Section of Gastroenterology and Hepatology,Department of Medicine,Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianliang","family":"Dai","sequence":"additional","affiliation":[{"name":"4002,Department of Biostatistics,University of Texas MD Anderson Cancer Center,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Innovations in Quality, Effectiveness and Safety (IQuESt),Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"4002,Department of Biostatistics,University of Texas MD Anderson Cancer Center,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5964-7579","authenticated-orcid":false,"given":"Hashem B.","family":"El\u2010Serag","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology and Hepatology,Department of Medicine,Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6715-3966","authenticated-orcid":false,"given":"Fasiha","family":"Kanwal","sequence":"additional","affiliation":[{"name":"Center for Innovations in Quality, Effectiveness and Safety (IQuESt),Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas,USA"},{"name":"Section of Gastroenterology and Hepatology,Department of Medicine,Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"issue":"1","key":"hep32244-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1053\/j.gastro.2010.09.038","article-title":"Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle\u2010aged population utilizing ultrasound and liver biopsy: a prospective study","volume":"140","year":"2011","journal-title":"Gastroenterology"},{"issue":"7","key":"hep32244-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.cgh.2017.12.048","article-title":"High prevalence of liver fibrosis among European adults with unknown liver disease: a population\u2010based study","volume":"16","year":"2018","journal-title":"Clin Gastroenterol 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