{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:25:05Z","timestamp":1787851505726,"version":"build-2784847793"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) remains a major complication in patients with chronic hepatitis B receiving nucleos(t)ide analogue (NA) therapy despite effective viral suppression. Although on\u2010treatment assessment of indirect fibrosis indices has been associated with HCC risk, the prognostic value of direct fibrosis markers, particularly type IV collagen 7S (4COL7S), during antiviral therapy remains poorly defined. We investigated whether on\u2010treatment 4COL7S predicts HCC development, with M2BPGi\u2010Qt evaluated as a supportive comparator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included 319 patients with chronic hepatitis B who initiated NA therapy. Serum 4COL7S and M2BPGi\u2010Qt were measured at baseline and 1\u00a0year after treatment initiation. The primary endpoint was HCC development. Landmark, Kaplan\u2013Meier, and multivariable Cox analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During a median follow\u2010up of 12.6\u00a0years, 45 patients (14.1%) developed HCC. Baseline 4COL7S and M2BPGi\u2010Qt did not significantly stratify cumulative HCC incidence. In contrast, elevated 1\u2010year levels of both markers were significantly associated with increased HCC risk. In multivariable analyses, 1\u2010year 4COL7S remained independently associated with subsequent HCC development after adjustment for baseline mPAGE\u2010B, 1\u2010year HBsAg\u2010HQ, and 1\u2010year HBcrAg (adjusted hazard ratio [HR], 1.167; 95% confidence interval [CI], 1.001\u20131.344;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.042). M2BPGi\u2010Qt showed consistent supportive findings (adjusted HR, 1.272; 95% CI, 1.101\u20131.468;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>On\u2010treatment 4COL7S was independently associated with subsequent HCC development and may serve as a novel direct fibrosis marker for long\u2010term risk stratification in NA\u2010treated chronic hepatitis B. M2BPGi\u2010Qt provided supportive prognostic information, underscoring the clinical relevance of reassessing residual fibrosis\u2010related risk after antiviral treatment initiation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hepr.70266","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:51:26Z","timestamp":1787849486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["On\u2010Treatment Reassessment of Type IV Collagen 7S and M2BPGi\u2010Qt Improves Long\u2010Term Hepatocellular Carcinoma Risk Stratification in Chronic Hepatitis B"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-4440","authenticated-orcid":false,"given":"Kazumi","family":"Yamasaki","sequence":"first","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideko","family":"Kozuru","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Sato","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Suehiro","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Motoyoshi","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2849-9057","authenticated-orcid":false,"given":"Yuki","family":"Kugiyama","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Saeki","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0331-7109","authenticated-orcid":false,"given":"Shinya","family":"Nagaoka","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2607-9381","authenticated-orcid":false,"given":"Atsumasa","family":"Komori","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-3403","authenticated-orcid":false,"given":"Hiroshi","family":"Yatsuhashi","sequence":"additional","affiliation":[{"name":"Clinical Research Center NHO Nagasaki Medical Center  Omura Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.035"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.01.007"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030949"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12688"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.08.028"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/hep.0000000000000752"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062051"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0168\u20108278(02)00429\u20104"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872\u2010034x.2011.00946.x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.14202"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8798"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1382293"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535\u2010024\u201002100\u20103"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535\u2010017\u20101424\u20100"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001219"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0276925"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.07.018"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13708"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.02.032"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz477"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.677920"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.02.040"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.70266","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hepr.70266","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.70266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:51:26Z","timestamp":1787849486000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.70266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":22,"alternative-id":["10.1111\/hepr.70266"],"URL":"https:\/\/doi.org\/10.1111\/hepr.70266","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"value":"1386-6346","type":"print"},{"value":"1872-034X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]},"assertion":[{"value":"2026-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"hepr.70266"}}