{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:09:59Z","timestamp":1790762999114,"version":"4.1.0"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Seidman Cancer Center","award":["17572.01.P0534.xxxxx.49275"],"award-info":[{"award-number":["17572.01.P0534.xxxxx.49275"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background &amp; aims<\/jats:title>\n<jats:p>Both non-alcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection commonly result in hepatic fibrosis and may lead to cirrhosis. This study aims to determine the incidence of HCC in patients with HCV or NAFLD complicated by advanced fibrosis, inferred from measurements of liver stiffness.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Using Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), we identified a nationwide cohort of patients with an existing diagnosis of HCV or NAFLD with liver transient elastography (TE) testing from 2015 to 2019. HCC cases, along with a random sample of non-HCC patients, were identified and validated, leading to calculation of incidence rates for HCC after adjustment for confounders.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>26,161 patients carried a diagnosis of HCV and 13,629 were diagnosed with NAFLD at the time of testing. In those with HCV, rates of HCC increased with liver stiffness with incidences of 0.28 (95% CI 0.24, 0.34), 0.93 (95% CI 0.72, 1.17), 1.28 (95% CI 0.89, 1.79), and 2.79 (95% CI 2.47, 3.14)\/100,000 person years for TE score ranges &lt;9.5 kPa, 9.5\u201312.5 kPa, 12.5\u201314.5 kPa and &gt;14.5 kPa, respectively, after a median follow-up of 2.3 years. HCC incidence also increased with higher TE liver stiffness measures in NAFLD after a median follow-up of 1.1 years.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In this retrospective cohort, the incidence of HCC in HCV and NAFLD increases with higher TE liver stiffness measures, confirming that advanced fibrosis portends risk in viral and non-viral fibrotic liver diseases. Additional comparative studies are needed to determine the optimal cut point of TE liver stiffness to inform HCC screening guidelines and approaches.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0280647","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T18:30:25Z","timestamp":1674585025000},"page":"e0280647","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma in hepatitis C infection and non-alcoholic fatty liver disease\u2013A population-based study"],"prefix":"10.1371","volume":"18","author":[{"given":"Perica","family":"Davitkov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-4925","authenticated-orcid":true,"given":"Kyle","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yngve","family":"Falck-Ytter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gjorgje","family":"Stojadinovikj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"Anthony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley Martin","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"pone.0280647.ref001","unstructured":"World Health Organization. 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update","volume":"53","author":"J Bruix","year":"2011","journal-title":"Hepatology"},{"key":"pone.0280647.ref008","first-page":"68","article-title":"Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases","author":"Staging Diagnosis","year":"2018","journal-title":"J Hepatol"},{"key":"pone.0280647.ref009","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jhep.2011.12.001","article-title":"EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma","volume":"56","author":"European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer","year":"2012","journal-title":"J Hepatol"},{"issue":"6","key":"pone.0280647.ref010","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1053\/j.gastro.2017.03.016","article-title":"American Gastroenterological Association institute technical review on the role of elastography in chronic liver 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