{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:18:59Z","timestamp":1793830739951,"version":"4.6.1"},"reference-count":32,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["107-2314-B-002-192-MY3"],"award-info":[{"award-number":["107-2314-B-002-192-MY3"]}]},{"name":"National Science and Technology Council","award":["109-2314-B-002-146-MY3"],"award-info":[{"award-number":["109-2314-B-002-146-MY3"]}]},{"name":"National Science and Technology Council","award":["110-2314-B-002-064-MY3"],"award-info":[{"award-number":["110-2314-B-002-064-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The value of metabolic-associated fatty liver disease (MAFLD) and its ability to assess hepatocellular carcinoma (HCC) risk remains uncertain for chronic hepatitis B (CHB). We evaluated the impacts of MAFLD and its coincidental metabolic abnormalities and related genetic predisposition on HCC incidence and mortality outcomes in CHB. We analyzed data from 1453 HBsAg-positive men (median age = 49.2 years at baseline) from a cohort of civil servants recruited from 1989\u20131992. MAFLD was defined as hepatic steatosis on ultrasound with obesity, diabetes, or metabolic dysfunction at baseline. During follow-up (median = 19.3 years), 105 HCC events occurred. MAFLD was not associated with HCC (adjusted hazard ratio (aHR) = 1.02) but was associated with a higher HBsAg seroclearance rate (aHR = 1.43). In mediation analysis, HBsAg seroclearance driven by hepatic steatosis explained 31.6% of the association between MAFLD and HCC. Antiviral treatment or fatty liver disease-associated genetic variants did not influence the MAFLD\u2013HCC association. In contrast, even after adjustment for MAFLD and the other metabolic abnormalities, diabetes (aHR = 2.28), obesity (aHR = 1.72), and metabolic dysfunction (aHR = 3.30) increased the risk of HCC (all p &lt; 0.030). The risk of HCC increased with the number of metabolic abnormalities (vs 0: aHR = 2.05 and 5.72 for 2 and \u2265 3 metabolic abnormalities, respectively), and the cumulative effect of metabolic abnormalities was found across subgroups categorized by hepatic steatosis as well as in participants both with and without HBsAg seroclearance. In conclusion, MAFLD was not associated with increased HCC incidence in CHB. A more informative assessment of HCC risk can be obtained by taking into account the number of metabolic abnormalities.<\/jats:p>","DOI":"10.3390\/cancers14236012","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T04:00:37Z","timestamp":1670385637000},"page":"6012","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Metabolic-Associated Fatty Liver Disease, Hepatitis B Surface Antigen Seroclearance, and Long-Term Risk of Hepatocellular Carcinoma in Chronic Hepatitis B"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-6236","authenticated-orcid":false,"given":"Ming-Whei","family":"Yu","sequence":"first","affiliation":[{"name":"Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei 10629, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6202-0993","authenticated-orcid":false,"given":"Chun-Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Jung","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Ting","family":"Hu","sequence":"additional","affiliation":[{"name":"Liver Center, Cathay General Hospital Medical Center, School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5196-7030","authenticated-orcid":false,"given":"Yi-Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Liver Center and Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan"},{"name":"Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease\u2014A global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J. 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