{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:33:36Z","timestamp":1790616816265,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T00:00:00Z","timestamp":1668902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003653","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2022ER090700"],"award-info":[{"award-number":["2022ER090700"]}],"id":[{"id":"10.13039\/501100003653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) and sarcopenia share insulin resistance as a common pathophysiology and have overlapping clinical manifestation of metabolic derangement; hence, it is difficult to differentiate the independent effect of sarcopenia on the development of NAFLD from concomitant metabolic disorders. Using a community\u2010based prospective cohort study, the contributions of low muscle mass and genetic risk factors to the development of NAFLD and NAFLD\u2010related hepatic fibrosis were investigated in the Korean population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prospective community\u2010based cohort study included 40\u201370\u2010year\u2010old adults, followed up biennially from 2001\u20132002 to 2017\u20132018. NAFLD was defined as a hepatic steatosis index of \u226536, and hepatic fibrosis was defined based on the fibrosis\u20104 index. Sex\u2010specific quartiles of body mass index (BMI)\u2010adjusted muscle mass were calculated (muscle mass\/BMI), and low muscle mass was defined as the lowest quartile (Q1). Cox proportional hazard models for incident NAFLD or hepatic fibrosis incorporating age, sex, BMI of \u226525\u00a0kg\/m<jats:sup>2<\/jats:sup>, metabolic syndrome and <jats:italic>PNPLA3<\/jats:italic> and <jats:italic>TM6SF2<\/jats:italic> risk alleles were used to assess the independent determinants for incident NAFLD and hepatic fibrosis among individuals with NAFLD at baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 4038 participants without NAFLD at baseline (mean age, 51.5\u00a0\u00b1\u00a08.8\u00a0years), 920 (22.8%) developed NAFLD during the 12\u2010year follow\u2010up period. As muscle mass decreased, the risk of NAFLD increased even after adjustment for age, sex, obesity, metabolic syndrome and <jats:italic>PNPLA3<\/jats:italic> and <jats:italic>TM6SF2<\/jats:italic> risk alleles [hazard ratio (HR) per quartile, 1.18, 95% confidence interval (CI), 1.11\u20131.27, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001]. <jats:italic>TM6SF2<\/jats:italic> also affected the risk of NAFLD development [HR 1.19, (95% CI, 1.00\u20131.40), <jats:italic>P<\/jats:italic>\u00a0=\u00a00.044].<\/jats:p><jats:p>Of the 1176 patients with NAFLD but without hepatic fibrosis at baseline, the incident of hepatic fibrosis was found in 51.8%, 44.7%, 42.6% and 41.0% in Q1, Q2, Q3 and Q4 of BMI\u2010adjusted muscle mass, respectively, during the follow\u2010up period (<jats:italic>P<\/jats:italic> for trend\u00a0=\u00a00.006). However, this trend lost its statistical significance when adjusted for confounders. The <jats:italic>PNPLA3<\/jats:italic> risk variant, but not the <jats:italic>TM6SF2<\/jats:italic> genotype, was an independent risk factor for developing hepatic fibrosis among patients with NAFLD (HR 1.17, 95% CI 1.04\u20131.32, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.010).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Both lower muscle mass index and genetic risk variants are important contributors to the development of NAFLD. In patients already diagnosed with NAFLD, however, <jats:italic>PNPLA3<\/jats:italic> confers a greater risk for hepatic fibrosis progression than lower muscle mass.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13125","type":"journal-article","created":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T23:34:57Z","timestamp":1668987297000},"page":"260-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Different effects of low muscle mass on the risk of non\u2010alcoholic fatty liver disease and hepatic fibrosis in a prospective cohort"],"prefix":"10.1002","volume":"14","author":[{"given":"Hun Jee","family":"Choe","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine  Seoul South Korea"},{"name":"Department of Internal Medicine, Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine  Seoul South Korea"},{"name":"Department of Internal Medicine, Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DongHo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo\u2010Heon","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine  Seoul South Korea"},{"name":"Department of Internal Medicine, Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-2656","authenticated-orcid":false,"given":"Bo Kyung","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine  Seoul South Korea"},{"name":"Department of Internal Medicine Seoul Metropolitan Government Boramae Medical Center  Seoul South 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