{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:58:28Z","timestamp":1753869508408,"version":"3.41.2"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011645","name":"Kaohsiung Medical University Chung-Ho Memorial Hospital","doi-asserted-by":"publisher","award":["KMUH110\u20100M03","KMUH111\u20101R05","KMU\u2010TC112B04","KMUH112\u20102R10"],"award-info":[{"award-number":["KMUH110\u20100M03","KMUH111\u20101R05","KMU\u2010TC112B04","KMUH112\u20102R10"]}],"id":[{"id":"10.13039\/501100011645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Chronic hepatitis B virus (HBV) infection is associated with potential complications of liver cirrhosis and hepatocellular carcinoma. To date, there are no effective and noninvasive clinical markers that can predict the risk of liver fibrosis early and accurately in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogs (NAs). This study aimed to investigate the association of circulating let\u20107b\/c\/g levels with the severity of hepatic fibrosis with a FIB\u20104 index of 1.5\u20132.9 in CHB patients. We conducted a retrospective longitudinal study in patients with CHB after 6\u2009months of NAs therapy to investigate whether serum let\u20107b\/c\/g levels can be monitored as an early biomarker for liver fibrogenesis based on multivariate logistic regression analyses. We also used the hepatic stellate cell line LX\u20102 treated with transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) to evaluate the suppression effect of let\u20107b\/c\/g on hepatic fibrogenesis. The study showed that circulating let\u20107b\/c\/g could predict 12\u2009months of antiviral treatment for HBV\u2010related significant fibrosis (FIB\u20104 index \u2265\u20092.9) at baseline and was significantly negatively correlated with the FIB\u20104 score. Moreover, let\u20107b\/c\/g could directly target the TGF\u2010\u03b2R1\u20133\u2032 untranslated region (3\u2032 UTR) and inhibit TGF\u2010\u03b2 induced p\u2010SMAD2 phosphorylation to reduce \u03b1\u2010smooth muscle actin levels, a fibrogenesis marker in LX\u20102 cells. These results confirm that let\u20107b\/c\/g could be a biomarker for monitoring HBV\u2010induced fibrogenesis.<\/jats:p>","DOI":"10.1002\/kjm2.70015","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T08:56:20Z","timestamp":1744707380000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating let\u20107 Predicts Hepatic Fibrogenesis of 12\u2010Month Post\u2010Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-1318","authenticated-orcid":false,"given":"Yi\u2010Shan","family":"Tsai","sequence":"first","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Cheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Hung","family":"Lin","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyng\u2010Yuan","family":"Jang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Ju","family":"Wei","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Health Management Center &amp; Department of Occupational Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010Ning","family":"Hsu","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng\u2010Hsuan","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Health Management Center &amp; Department of Occupational Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Yen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih\u2010Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zu\u2010Yau","family":"Lin","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Lun","family":"Yeh","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease National Sun Yat\u2010sen University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung\u2010Feng","family":"Huang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Health Management Center &amp; Department of Occupational Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jee\u2010Fu","family":"Huang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Lung","family":"Yu","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Health Management Center &amp; Department of Occupational Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease National Sun Yat\u2010sen University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan\u2010Long","family":"Chuang","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia\u2010Yen","family":"Dai","sequence":"additional","affiliation":[{"name":"Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Health Management Center &amp; Department of Occupational Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Faculty of Internal Medicine, College of Medicine and Drug Development and Value Creation Research Center Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease National Sun Yat\u2010sen University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0186-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00124-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280404"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001453"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01091-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2004.11.009"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105728"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-022-00799-z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3816-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep23237"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.12.043"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201208082"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28660"},{"issue":"5","key":"e_1_2_9_15_1","first-page":"3935","article-title":"let\u20107a Suppresses Liver Fibrosis via TGFbeta\/SMAD Signaling Transduction Pathway","volume":"17","author":"Zhang Y.","year":"2019","journal-title":"Experimental and Therapeutic Medicine"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14474"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29802"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.07.019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144945"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-016-9760-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.10.021"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.372"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.17.5353"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13665"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon.7581"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00458.2014"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-022-02575-5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.06.001"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101828"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-011-0223-0"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.12.024"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021428"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0331"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327202"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-022-00317-9"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40959-7"}],"container-title":["The Kaohsiung Journal of Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.70015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T12:15:15Z","timestamp":1750940115000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/kjm2.70015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,29]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/kjm2.70015"],"URL":"https:\/\/doi.org\/10.1002\/kjm2.70015","archive":["Portico"],"relation":{},"ISSN":["1607-551X","2410-8650"],"issn-type":[{"type":"print","value":"1607-551X"},{"type":"electronic","value":"2410-8650"}],"subject":[],"published":{"date-parts":[[2025,3,29]]},"assertion":[{"value":"2024-12-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70015"}}