{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T23:43:46Z","timestamp":1785714226403,"version":"3.56.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22fk0210064"],"award-info":[{"award-number":["JP22fk0210064"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Patients with advanced fibrosis are at risk for developing hepatocellular carcinoma (HCC) even after hepatitis C virus (HCV) elimination. We previously reported that serum fucosylated haptoglobin (Fuc-Hp) levels increase as the disease progresses from chronic hepatitis to cirrhosis and then HCC. However, it remains unclear whether serum Fuc-Hp levels can stratify the risk of HCC occurrence after a sustained virological response (SVR) is achieved with direct-acting antivirals (DAAs) in patients with advanced liver fibrosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Among 3,550 patients with chronic hepatitis C treated with DAAs at Osaka University Hospital and related hospitals, the stored sera of 140 patients who were diagnosed with F3 or F4 by liver biopsy before DAA treatment, achieved SVR, and had no history of HCC were available at both baseline and the end of treatment (EOT). We measured the Fuc-Hp levels in these samples.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The median serum levels of Fuc-Hp at EOT were significantly lower than those at baseline. During the 54.4-month follow-up period, 16 of 140 patients developed HCC. Multivariate Cox proportional hazards analysis revealed that high Fuc-Hp at EOT, high body mass index (BMI), and low albumin at EOT were independent risk factors for HCC occurrence. Patients with all three factors\u2014high Fuc-Hp, high BMI, and low albumin\u2014had a higher incidence of HCC than patients without these factors.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>High serum Fuc-Hp levels at EOT were an independent risk factor for HCC occurrence after SVR. Combined with BMI and albumin, Fuc-Hp can stratify the risk of HCC occurrence among those with advanced fibrosis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0279416","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T18:26:51Z","timestamp":1671647211000},"page":"e0279416","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Fucosylated haptoglobin is a novel predictive marker of hepatocellular carcinoma after hepatitis C virus elimination in patients with advanced liver fibrosis"],"prefix":"10.1371","volume":"17","author":[{"given":"Kumiko","family":"Shirai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Hikita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-607X","authenticated-orcid":true,"given":"Ryotaro","family":"Sakamori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Doi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadatsugu","family":"Sakane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-902X","authenticated-orcid":true,"given":"Yoshihiro","family":"Kamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-2922","authenticated-orcid":true,"given":"Kazuhiro","family":"Murai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kodama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutoshi","family":"Nozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naruyasu","family":"Kakita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuho","family":"Imanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Sakakibara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohide","family":"Tatsumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9430-2362","authenticated-orcid":true,"given":"Eiji","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5036-3457","authenticated-orcid":true,"given":"Tetsuo","family":"Takehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"issue":"12","key":"pone.0279416.ref001","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/j.cgh.2016.07.001","article-title":"Safety and Effectiveness of Direct-Acting Antiviral Agents for Treatment of Patients With Chronic Hepatitis C Virus Infection and Cirrhosis","volume":"14","author":"R Maan","year":"2016","journal-title":"Clin Gastroenterol Hepatol"},{"key":"pone.0279416.ref002","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/liv.13638","article-title":"Treatment of hepatitis C: Results in real life","volume":"381","author":"C. 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