{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:48:37Z","timestamp":1791600517439,"version":"4.3.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Merck Sharp & Dohme and Gilead Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Direct-acting antiviral (DAA) treatment has revolutionized hepatitis C virus (HCV) care. We aimed to evaluate the risk for the development of hepatocellular carcinoma (HCC) in patients aged 75\u201384 years with chronic hepatitis C after HCV elimination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter cohort study included 2405 consecutive patients with chronic hepatitis C without a history of HCC who achieved HCV elimination by DAAs. Patients in whom HCC developed within 1 year of DAA initiation were excluded. Propensity score matching analysis was used to evaluate differences in HCC risk between patients aged 75\u201384 versus 60\u201374 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median observational period was 3.5 years. Among patients aged 75\u201384 years with a high Fibrosis-4 (FIB-4) index (\u22653.25 at baseline), there was no significant difference in the annual incidence of HCCs between groups with an FIB-4 index \u22653.25 (2.75 per 100 person-years [PY]) versus &amp;lt;3.25 (2.16 per 100 PY) at 12 weeks after the end of treatment, unlike the results in those aged 60\u201374 years (3.61 and 1.51 per 100 PY, respectively) (adjusted hazard ratio, 2.20; P = .04). In 495 pairs matched by propensity score matching, in patients without cirrhosis, the cumulative HCC incidence was significantly higher in the 75\u201384-year than in the 60\u201374-year age group (P = .04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Older patients aged 75\u201384 years remained at high risk for the development of HCC, even after HCV elimination and the improvement of the FIB-4 index to &amp;lt;3.25.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiaa359","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:10:10Z","timestamp":1592478610000},"page":"431-440","source":"Crossref","is-referenced-by-count":13,"title":["Development of Hepatocellular Carcinoma in Patients Aged 75\u201384 Years With Chronic Hepatitis C Treated With Direct-Acting Antivirals"],"prefix":"10.1093","volume":"226","author":[{"given":"Eiichi","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of General Internal Medicine, Kyushu University Hospital , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Nomura","sequence":"additional","affiliation":[{"name":"The Center for Liver Disease, Shin-Kokura Hospital , Kitakyushu , Japan"},{"name":"Department of Internal Medicine, Haradoi Hospital , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Nakamuta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Furusyo","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Kyushu University Hospital , Fukuoka , Japan"},{"name":"General Internal Medicine, Taihaku Avenue Clinic , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Kajiwara","sequence":"additional","affiliation":[{"name":"Kajiwara Clinic , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazufumi","family":"Dohmen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chihaya Hospital , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kitakyushu Municipal Medical Center , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aritsune","family":"Ooho","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Steel Memorial Yawata Hospital , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Azuma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Kyushu Central Hospital , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hamanomachi Hospital , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeaki","family":"Satoh","sequence":"additional","affiliation":[{"name":"Center for Liver Disease, National Hospital Organization Kokura Medical Center , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimasa","family":"Koyanagi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Fukuoka City Hospital , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Ichiki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, JCHO Kyushu Hospital , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Kuniyoshi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kyushu Rosai Hospital , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiko","family":"Yanagita","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Saiseikai Karatsu Hospital , Karatsu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Amagase","sequence":"additional","affiliation":[{"name":"Amagase Clinic , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyushu Railway Memorial Hospital , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kyushu Cancer Center , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Kyushu General Internal Medicine Center, Haradoi Hospital , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Kyushu University Liver Disease Study (KULDS) Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"2022082618083524400_CIT0001","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1016\/j.jhep.2014.07.027","article-title":"Global epidemiology and genotype distribution of the hepatitis C virus infection","volume":"61","author":"Gower","year":"2014","journal-title":"J Hepatol"},{"key":"2022082618083524400_CIT0002","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":"2022082618083524400_CIT0003","doi-asserted-by":"crossref","first-page":"637","DOI":"10.7326\/M16-2575","article-title":"Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review","volume":"166","author":"Falade-Nwulia","year":"2017","journal-title":"Ann Intern Med"},{"key":"2022082618083524400_CIT0004","doi-asserted-by":"crossref","first-page":"100237","DOI":"10.1016\/j.eclinm.2019.12.007","article-title":"Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: a systematic literature review and meta-analysis","volume":"18","author":"Zoratti","year":"2020","journal-title":"EClinicalMedicine"},{"key":"2022082618083524400_CIT0005","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/j.1440-1746.2011.06965.x","article-title":"Evaluation of the adverse effect of premature discontinuation of pegylated interferon \u03b1-2b and ribavirin treatment for chronic hepatitis C virus infection: results from Kyushu University Liver Disease Study","volume":"27","author":"Ogawa","year":"2012","journal-title":"J Gastroenterol Hepatol"},{"key":"2022082618083524400_CIT0006","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jhep.2016.11.012","article-title":"Efficacy and tolerability of an IFN-free regimen with DCV\/ASV for elderly patients infected with HCV genotype 1B","volume":"66","author":"Toyoda","year":"2017","journal-title":"J Hepatol"},{"key":"2022082618083524400_CIT0007","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.antiviral.2018.10.003","article-title":"Elbasvir plus grazoprevir for patients with chronic hepatitis C genotype 1: a multicenter, real-world cohort study focusing on chronic kidney disease","volume":"159","author":"Ogawa","year":"2018","journal-title":"Antiviral Res"},{"key":"2022082618083524400_CIT0008","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/nrgastro.2016.176","article-title":"Global epidemiology and burden of HCV infection and HCV-related disease","volume":"14","author":"Thrift","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2022082618083524400_CIT0009","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1017\/S0950268814000478","article-title":"Changes in hepatitis C virus genotype distribution in Japan","volume":"142","author":"Toyoda","year":"2014","journal-title":"Epidemiol Infect"},{"key":"2022082618083524400_CIT0010","doi-asserted-by":"crossref","first-page":"817","DOI":"10.7326\/0003-4819-157-9-201211060-00529","article-title":"Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention","volume":"157","author":"Smith","year":"2012","journal-title":"Ann Intern Med"},{"key":"2022082618083524400_CIT0011","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S0140-6736(96)07642-8","article-title":"Natural history of liver fibrosis progression in patients with chronic hepatitis C: the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups","volume":"349","author":"Poynard","year":"1997","journal-title":"Lancet"},{"key":"2022082618083524400_CIT0012","first-page":"S47","article-title":"Fibrosis and disease progression in hepatitis C","volume":"36","author":"Marcellin","year":"2002","journal-title":"Hepatology"},{"key":"2022082618083524400_CIT0013","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.jhep.2018.07.024","article-title":"Development of models estimating the risk of hepatocellular carcinoma after antiviral treatment for hepatitis C","volume":"69","author":"Ioannou","year":"2018","journal-title":"J Hepatol"},{"key":"2022082618083524400_CIT0014","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1053\/j.gastro.2019.07.040","article-title":"Direct-acting antiviral therapy for hepatitis C virus infection is associated with increased survival in patients with a history of hepatocellular carcinoma","volume":"157","author":"Singal","year":"2019","journal-title":"Gastroenterology"},{"key":"2022082618083524400_CIT0015","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/hep.30823","article-title":"Long-term risk of hepatocellular carcinoma in HCV patients treated with direct acting antiviral agents","volume":"71","author":"Kanwal","year":"2020","journal-title":"Hepatology"},{"key":"2022082618083524400_CIT0016","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/ggi.13118","article-title":"Redefining the elderly as aged 75 years and older: proposal from the Joint Committee of Japan Gerontological Society and the Japan Geriatrics Society","volume":"17","author":"Ouchi","year":"2017","journal-title":"Geriatr Gerontol Int"},{"key":"2022082618083524400_CIT0017","doi-asserted-by":"crossref","first-page":"807","DOI":"10.7326\/0003-4819-158-11-201306040-00005","article-title":"Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review","volume":"158","author":"Chou","year":"2013","journal-title":"Ann Intern Med"},{"key":"2022082618083524400_CIT0018","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/00031305.1985.10479383","article-title":"Constructing a control-group using multivariate matched sampling methods that incorporate the propensity score","volume":"39","author":"Rosenbaum","year":"1985","journal-title":"Am Stat"},{"key":"2022082618083524400_CIT0019","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/ajg.2016.453","article-title":"Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis","volume":"112","author":"McPherson","year":"2017","journal-title":"Am J Gastroenterol"},{"key":"2022082618083524400_CIT0020","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2019.07.033","article-title":"Increased risk for hepatocellular carcinoma persists up to 10 years after HCV eradication in patients with baseline cirrhosis or high FIB-4 scores","volume":"157","author":"Ioannou","year":"2019","journal-title":"Gastroenterology"},{"key":"2022082618083524400_CIT0021","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/apt.14380","article-title":"Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment","volume":"47","author":"Ogawa","year":"2018","journal-title":"Aliment Pharmacol Ther"},{"key":"2022082618083524400_CIT0022","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/apt.15006","article-title":"Serum M2BPGi level and risk of hepatocellular carcinoma after oral anti-viral therapy in patients with chronic hepatitis B","volume":"48","author":"Hsu","year":"2018","journal-title":"Aliment Pharmacol Ther"},{"key":"2022082618083524400_CIT0023","doi-asserted-by":"crossref","first-page":"407","DOI":"10.7326\/M14-1152","article-title":"Cost-effectiveness of novel regimens for the treatment of hepatitis C virus","volume":"162","author":"Najafzadeh","year":"2015","journal-title":"Ann Intern Med"},{"key":"2022082618083524400_CIT0024","doi-asserted-by":"crossref","first-page":"djx030","DOI":"10.1093\/jnci\/djx030","article-title":"Annual report to the nation on the status of cancer, 1975\u20132014, featuring survival","volume":"109","author":"Jemal","year":"2017","journal-title":"J Natl Cancer Inst"},{"key":"2022082618083524400_CIT0025","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/S0140-6736(18)32335-3","article-title":"Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"Kyu","year":"2018","journal-title":"Lancet"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaa359\/33509095\/jiaa359.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/226\/3\/431\/45583743\/jiaa359.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/226\/3\/431\/45583743\/jiaa359.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T22:43:27Z","timestamp":1723070607000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/226\/3\/431\/5862583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,25]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,6,25]]},"published-print":{"date-parts":[[2022,8,26]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaa359","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,8,1]]},"published":{"date-parts":[[2020,6,25]]}}}