{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:29:36Z","timestamp":1790022576564,"version":"4.0.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T00:00:00Z","timestamp":1551312000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hepatol Int"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1007\/s12072-019-09939-2","type":"journal-article","created":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T03:28:18Z","timestamp":1551324498000},"page":"293-301","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study"],"prefix":"10.1007","volume":"13","author":[{"given":"Tatsuya","family":"Ide","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-9543","authenticated-orcid":false,"given":"Hironori","family":"Koga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahito","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yatsuhashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobito","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Nakamuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Oeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Shakado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Sakisaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Yoshimaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Honma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Seike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuji","family":"Maeshiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Miuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Nakao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Mawatari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Ido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Takami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Sohda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuyuki","family":"Kakuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Torimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,28]]},"reference":[{"key":"9939_CR1","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1016\/j.jhep.2014.07.027","volume":"61","author":"E Gower","year":"2014","unstructured":"Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61:S45\u2013S57.","journal-title":"J Hepatol"},{"key":"9939_CR2","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/hepr.12393","volume":"45","author":"N Hiramatsu","year":"2015","unstructured":"Hiramatsu N, Oze T, Takehara T. Suppression of hepatocellular carcinoma development in hepatitis C patients given interferon-based antiviral therapy. Hepatol Res. 2015;45:152\u2013161.","journal-title":"Hepatol Res"},{"key":"9939_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1002\/hep.27890","volume":"62","author":"Y Tanaka","year":"2015","unstructured":"Tanaka Y, Nishida N, Sugiyama M. Safety and tolerability of ledipasvir\/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials. Hepatology. 2015;62:25\u201330.","journal-title":"Hepatology"},{"key":"9939_CR4","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1002\/hep.28467","volume":"64","author":"P Kwo","year":"2016","unstructured":"Kwo P, Gitlin N, Nahass R, Bernstein D, Etzkorn K, Rojter S, et al. Simeprevir plus sofosbuvir (12 and 8 weeks) in HCV genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. Hepatology. 2016;64:370\u2013380.","journal-title":"Hepatology"},{"key":"9939_CR5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jhep.2016.08.021","volume":"66","author":"S Pol","year":"2017","unstructured":"Pol S, Lucier S, de L\u00e9dinghen V, Zoulim F, Dorival-Mouly C, et al. Safety and efficacy of the combination daclatasvir-sofosbuvir in HCV genotype 1-monoinfected patients. J Hepatol. 2017;66:39\u201347.","journal-title":"J Hepatol"},{"key":"9939_CR6","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1053\/j.gastro.2018.04.008","volume":"155","author":"V Calvaruso","year":"2018","unstructured":"Calvaruso V, Cabibbo G, Cacciola I, Petta S, Madonia S, Bellia A, Tin\u00e8 F, et al. Incidence of Hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroenterology. 2018;155:411\u2013421.","journal-title":"Gastroenterology"},{"key":"9939_CR7","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.jhep.2016.04.008","volume":"65","author":"M Reig","year":"2016","unstructured":"Reig M, Mari\u00f1o Z, Perell\u00f3 C, I\u00f1arrairaegui M, Ribeiro A, Lens S, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65:719\u2013726.","journal-title":"J Hepatol"},{"key":"9939_CR8","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.jhep.2016.06.015","volume":"65","author":"F Conti","year":"2016","unstructured":"Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65:727\u2013733.","journal-title":"J Hepatol"},{"key":"9939_CR9","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1016\/j.jhep.2017.11.011","volume":"68","author":"Y Nakao","year":"2017","unstructured":"Nakao Y, Hashimoto S, Abiru S, Komori A, Yamasaki K, Nagaoka S, et al. Rapidly growing, moderately differentiated HCC: A clinicopathological characteristic of HCC occurrence after IFN-free DAA therapy? J Hepatol. 2017;68:854\u2013855.","journal-title":"J Hepatol"},{"key":"9939_CR10","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1053\/jhep.2003.50346","volume":"38","author":"CT Wai","year":"2003","unstructured":"Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518-526.","journal-title":"Hepatology"},{"key":"9939_CR11","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.21178","volume":"43","author":"RK Sterling","year":"2006","unstructured":"Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection. Hepatology. 2006;43:1317\u20131325.","journal-title":"Hepatology"},{"key":"9939_CR12","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0168-8227(01)00365-5","volume":"55","author":"T Kuzuya","year":"2002","unstructured":"Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, et al. Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract 2002;55:65-85.","journal-title":"Diabetes Res Clin Pract"},{"issue":"Suppl. 1","key":"9939_CR13","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/liv.13659","volume":"38","author":"B Roche","year":"2018","unstructured":"Roche B, Coilly A, Duclos-Vallee JC, Samuel D. The impact of treatment of hepatitis C with DAAs on the occurrence of HCC. Liver Int. 2018;38(Suppl. 1):139\u2013145.","journal-title":"Liver Int"},{"key":"9939_CR14","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.jhep.2017.07.025","volume":"67","author":"R Waziry","year":"2017","unstructured":"Waziry R, Hajarizadeh B, Grebely J, Amin J, Law M, Danta M, et al. Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression. J Hepatol. 2017;67:1204\u20131212.","journal-title":"J Hepatol"},{"key":"9939_CR15","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1053\/j.gastro.2017.06.012","volume":"153","author":"F Kanwal","year":"2017","unstructured":"Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, El-Serag HB, et al. Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents. Gastroenterology. 2017;153:996\u20131005.","journal-title":"Gastroenterology"},{"key":"9939_CR16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jhep.2017.08.030","volume":"68","author":"GN Ioannou","year":"2018","unstructured":"Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2018;68:25\u2013322.","journal-title":"J Hepatol"},{"issue":"Suppl 1","key":"9939_CR17","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1053\/j.gastro.2004.09.014","volume":"127","author":"G Fattovich","year":"2004","unstructured":"Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(Suppl 1):S35\u201350.","journal-title":"Gastroenterology"},{"key":"9939_CR18","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1002\/hep.510290439","volume":"29","author":"K Ikeda","year":"1999","unstructured":"Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124\u20131130.","journal-title":"Hepatology"},{"key":"9939_CR19","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1002\/hep.510270529","volume":"27","author":"A Kasahara","year":"1998","unstructured":"Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology. 1998;27:1394\u20131402.","journal-title":"Hepatology"},{"key":"9939_CR20","doi-asserted-by":"publisher","first-page":"174","DOI":"10.7326\/0003-4819-131-3-199908030-00003","volume":"131","author":"H Yoshida","year":"1999","unstructured":"Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of hepatocarcinogenesis by interferon therapy. Ann Intern Med 1999;131:174-181.","journal-title":"Ann Intern Med"},{"key":"9939_CR21","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1038\/oby.2007.218","volume":"15","author":"Y Doi","year":"2007","unstructured":"Doi Y, Kubo M, Yonemoto K, Ninomiya T, Iwase M, Tanizaki Y, et al. Liver enzymes as a predictor for incident diabetes in a Japanese population: the Hisayama study. Obesity 2007;15:1841\u20131850.","journal-title":"Obesity"},{"key":"9939_CR22","doi-asserted-by":"publisher","first-page":"134","DOI":"10.5582\/ddt.2014.01025","volume":"8","author":"Z Wang","year":"2014","unstructured":"Wang Z, Song P, Xia J, Inagaki Y, Tang W, Kokudo N. Can gamma-glutamyl transferase levels contribute to a better prognosis for patients with hepatocellular carcinoma? Drug Discov Ther. 2014;8:134\u2013138.","journal-title":"Drug Discov Ther."}],"container-title":["Hepatology International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12072-019-09939-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-019-09939-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-019-09939-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T19:28:41Z","timestamp":1582831721000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12072-019-09939-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,28]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["9939"],"URL":"https:\/\/doi.org\/10.1007\/s12072-019-09939-2","relation":{},"ISSN":["1936-0533","1936-0541"],"issn-type":[{"value":"1936-0533","type":"print"},{"value":"1936-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,28]]},"assertion":[{"value":"26 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Akio Ido has COI as follows: (1) Speaking fees or honoraria; AbbVie GK, Bristol Myers Squibb Co. Ltd., Gilead Sciences Inc., and Eisai Co. Ltd. (2) Research grants; AbbVie GK, Otsuka Pharmaceutical Co. Ltd., MSD K.K., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Astellas Pharmaceutical Inc., and Takeda Pharmaceutical Co. Ltd. The other authors disclose no conflicts.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest:"}},{"value":"The protocol was approved by all hospital institutional review boards and carried out in compliance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all participating patients.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}