{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T08:58:23Z","timestamp":1767085103448,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Direct-acting antiviral agents (DAAs) have improved sustained virologic response (SVR) rates in patients with chronic hepatitis C virus (HCV) infection. Our aim was to elucidate the occurrence of hepatocellular carcinoma (HCC) and to compare the outcomes of patients aged 75 years or older (older group) with those of patients younger than 75 years (younger group) after SVR. Materials and Methods: Among 441 patients treated with interferon-free DAA combinations, a total of 409 SVR patients were analyzed. We compared the two age groups in terms of HCC incidence and mortality rates. Results: Older and younger groups consisted of 68 and 341 patients, respectively. Occurrence of HCC after SVR did not differ between the two groups of patients with a history of HCC. Occurrence of HCC after SVR was observed more in younger patients without a history of HCC (p &lt; 0.01). Although older patients without a history of HCC had a higher mortality rate (p &lt; 0.01), their causes of death were not associated with liver diseases. Among younger patients without a history of HCC, none died. Conclusions: After SVR, liver disease may not be a prognostic factor in older HCV patients without a history of HCC.<\/jats:p>","DOI":"10.3390\/medicina57080761","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T12:18:31Z","timestamp":1627388311000},"page":"761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Follow-Up of Patients Who Achieved Sustained Virologic Response after Interferon-Free Treatment against Hepatitis C Virus: Focus on Older Patients"],"prefix":"10.3390","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3926-5076","authenticated-orcid":false,"given":"Kazushige","family":"Nirei","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-5385","authenticated-orcid":false,"given":"Tatsuo","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5118-4397","authenticated-orcid":false,"given":"Ryota","family":"Masuzaki","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiko","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1056\/NEJMoa1316366","article-title":"Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection","volume":"370","author":"Afdhal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1056\/NEJMoa1402454","article-title":"Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection","volume":"370","author":"Afdhal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1007\/s00535-018-1455-1","article-title":"Real-world efficacy and safety of ledipasvir and sofosbuvir in patients with hepatitis C virus genotype 1 infection: A nationwide multicenter study by the Japanese Red Cross Liver Study Group","volume":"53","author":"Tsuji","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/jmv.24663","article-title":"Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection","volume":"89","author":"Kobayashi","year":"2017","journal-title":"J. Med. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/jgh3.12088","article-title":"Real-world safety and efficacy of sofosbuvir and ledipasvir for elderly patients","volume":"2","author":"Tamai","year":"2018","journal-title":"JGH Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S1473-3099(15)70099-X","article-title":"Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: An open-label, randomised, phase 3 trial","volume":"15","author":"Mizokami","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/jvh.12549","article-title":"Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir\/Sofosbuvir Containing Regimens in Phase 3 Studies","volume":"23","author":"Mizokami","year":"2016","journal-title":"J. Viral Hepat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/jvh.12312","article-title":"Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: An open-label, phase 3 trial","volume":"21","author":"Omata","year":"2014","journal-title":"J. Viral Hepat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"418","DOI":"10.7150\/ijms.15519","article-title":"Daclatasvir plus Asunaprevir Treatment for Real-World HCV Genotype 1-Infected Patients in Japan","volume":"13","author":"Kanda","year":"2016","journal-title":"Int. J. Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1002\/hep.27705","article-title":"Randomized trial of interferon- and ribavirin-free ombitasvir\/paritaprevir\/ritonavir in treatment-experienced hepatitis C virus-infected patients","volume":"61","author":"Chayama","year":"2015","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12072-018-9915-5","article-title":"APASL clinical practice recommendation: How to treat HCV-infected patients with renal impairment?","volume":"13","author":"Kanda","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.21873\/anticanres.13535","article-title":"Follow-up Results of HCV GT2 Patients after Sofosbuvir\/Ribavirin Therapy: Careful Attention to Occurrence of HCC","volume":"39","author":"Kaneko","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(18)32111-1","article-title":"Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: A prospective cohort study","volume":"393","author":"Carrat","year":"2019","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.15403\/jgld.2014.1121.281.hpc","article-title":"Predictive factors for hepatocellular carcinoma occurrence or recurrence after direct-acting antiviral agents in patients with chronic hepatitis C","volume":"28","author":"Yoshimasu","year":"2019","journal-title":"J. Gastrointest. Liver Dis. JGLD"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/ggi.13118","article-title":"Joint Committee of Japan Gerontological Society (JGLS); Japan Geriatrics Society (JGS) on the Definition and Classification of the Elderly. 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":"ref_16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1128\/jcm.35.1.201-207.1997","article-title":"New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a","volume":"35","author":"Ohno","year":"1997","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/hep.21669","article-title":"FIB-4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest","volume":"46","author":"Mallet","year":"2007","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"787","DOI":"10.2169\/internalmedicine.56.7948","article-title":"Ventricular Tachycardia as a Complication of Ledipasvir and Sofosbuvir Treatment for HCV Infection","volume":"56","author":"Nirei","year":"2017","journal-title":"Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1002\/hep.29707","article-title":"The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study","volume":"67","author":"Li","year":"2018","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1053\/j.gastro.2017.06.012","article-title":"Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents","volume":"153","author":"Kanwal","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/hep.23691","article-title":"Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection","volume":"52","author":"Asahina","year":"2010","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s12072-019-09988-7","article-title":"APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation","volume":"13","author":"Kanda","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jhep.2016.04.008","article-title":"Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy","volume":"65","author":"Reig","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.jhep.2016.06.019","article-title":"Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis","volume":"65","author":"Cheung","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1111\/liv.13456","article-title":"Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C","volume":"37","author":"Virlogeux","year":"2017","journal-title":"Liver Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1007\/s10620-017-4739-z","article-title":"Direct-Acting Antivirals Decreased Tumor Recurrence After Initial Treatment of Hepatitis C Virus-Related Hepatocellular Carcinoma","volume":"62","author":"Ikeda","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.dld.2018.10.014","article-title":"Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals","volume":"51","author":"Lleo","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jhep.2017.05.028","article-title":"Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C","volume":"67","author":"Nagata","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/hep.29408","article-title":"Impact of Sustained Virologic Response with Direct-Acting Antiviral Treatment on Mortality in Patients with Advanced Liver Disease","volume":"69","author":"Backus","year":"2019","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"299","DOI":"10.7326\/0003-4819-138-4-200302180-00008","article-title":"Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus","volume":"138","author":"Shiratori","year":"2003","journal-title":"Ann. Intern. Med."},{"key":"ref_32","unstructured":"(2021, July 24). National Cancer Center Japan. Available online: https:\/\/ganjoho.jp\/reg_stat\/statistics\/stat\/cancer\/8_liver.html#anchor4."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/8\/761\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:35:44Z","timestamp":1760164544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/8\/761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,27]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["medicina57080761"],"URL":"https:\/\/doi.org\/10.3390\/medicina57080761","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2021,7,27]]}}}