{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:52:30Z","timestamp":1776707550463,"version":"3.51.2"},"reference-count":46,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"unspecified","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Echosens LTD"},{"name":"NIHR Biomedical Research Centre, Southampton","award":["NIHR203319"],"award-info":[{"award-number":["NIHR203319"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,2,7]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Hepatocellular carcinoma (HCC) is expected to become the third most common cause of cancer death worldwide by 2030. The increase in HCC is in large part due to the rising prevalence of risk factors such as type 2 diabetes mellitus (T2DM). Up to 1 in 20 people living with T2DM have liver cirrhosis, and they have a 1% to 2% incidence of HCC per year. Patients with cirrhosis enter surveillance for HCC to identify early-stage, curable tumours. A diagnosis of T2DM does not mandate testing to identify patients with cirrhosis, with testing restricted to those with additional risks. There has never been a trial and nested cost-effectiveness evaluation comparing screening all patients with T2DM for cirrhosis against usual care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>The study will use a multi-centre, unblinded individual randomised controlled trial design. The aim will be to determine the effectiveness and cost-effectiveness of screening all adults with T2DM to identify those at high risk of HCC. The recruitment strategy has been supported by patient and public involvement (PPI). Participants will be identified via an automated search of primary care records and invited to participate via text. 320 participants will be randomised for screening. The screening will include measurement of bio-markers for liver fibrosis (ELF and Fib-4) and vibration-controlled transient elastography. Another 320 participants will be randomised to standard care. Demographic and medical history data will be collected at baseline from all participants. Outcome data will be collected remotely from healthcare records. The primary outcome is the proportion of participants in each arm who are referred to HCC surveillance following testing for liver disease within 12\u2009months of randomisation. The results will be used to calculate the incremental cost-effectiveness ratio of screening via a Markov model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The results of this study will be presented directly to National Health Service England. Additional dissemination via conference proceedings and publication will be supported by our PPI team. Ethical approval was granted by the West of Scotland Research Ethics Service on 2 August 2023, REC reference 23\/WS\/0102.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"isrctn\" xlink:href=\"ISRCTN17017677\">ISRCTN17017677<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-088043","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:16:59Z","timestamp":1741331819000},"page":"e088043","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Screening to identify people with type 2 diabetes at risk of liver cancer in primary care: a randomised controlled trial protocol"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"isrctn17017677","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0850-5575","authenticated-orcid":false,"given":"Ryan M","family":"Buchanan","sequence":"first","affiliation":[{"name":"University of Southampton Faculty of Medicine, Southampton, UK"},{"name":"University Hospital Southampton NHS Foundation Trust, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2436-1906","authenticated-orcid":false,"given":"Tina","family":"Reinson","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Division, University of Southampton Faculty of Medicine, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josh","family":"Bilson","sequence":"additional","affiliation":[{"name":"University of Southampton Faculty of Medicine, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazel","family":"Woodland","sequence":"additional","affiliation":[{"name":"Salisbury District Hospital NHS Foundation Trust, Salisbury, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinonso","family":"Nwoguh","sequence":"additional","affiliation":[{"name":"University of Southampton Faculty of Medicine, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0318-7670","authenticated-orcid":false,"given":"Keith","family":"Cooper","sequence":"additional","affiliation":[{"name":"Southampton Health Technology Assessment Centre, University of Southampton, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Harris","sequence":"additional","affiliation":[{"name":"University of Southampton Faculty of Medicine, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Malone","sequence":"additional","affiliation":[{"name":"The Old Fire Station Surgery, Woolston, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher D","family":"Byrne","sequence":"additional","affiliation":[{"name":"University of Southampton Faculty of Medicine, Southampton, UK"},{"name":"NIHR Southampton Biomedical Research Centre, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"2025101812275544000_15.3.e088043.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30431-9"},{"key":"2025101812275544000_15.3.e088043.2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/dmrr.1291","article-title":"Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta-analysis","volume":"28","author":"Wang","year":"2012","journal-title":"Diabetes Metab Res Rev"},{"key":"2025101812275544000_15.3.e088043.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.08.021"},{"key":"2025101812275544000_15.3.e088043.4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26986"},{"key":"2025101812275544000_15.3.e088043.5","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1001\/jamaoncol.2017.3055","article-title":"The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015","volume":"3","author":"Akinyemiju","year":"2017","journal-title":"JAMA Oncol"},{"key":"2025101812275544000_15.3.e088043.6","unstructured":"European Association for the Study of the Liver (EASL) . 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