{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:04:56Z","timestamp":1789535096079,"version":"build-2803163510"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic hepatitis B (CHB) frequently coexists with metabolic dysfunction\u2013associated fatty liver disease (MAFLD), yet the impact of MAFLD on hepatitis B virus (HBV) replication remains incompletely understood. We aimed to investigate the association between MAFLD and HBV DNA levels and to provide biological context through integrative transcriptomic analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed a large retrospective cohort of patients with CHB and assessed the association between MAFLD and serum HBV DNA levels using linear regression models. HBV DNA was analyzed as a continuous outcome after log10 transformation. To provide molecular context for the clinical findings, weighted gene co-expression network analysis (WGCNA) was performed in an independent HBV liver transcriptomic dataset to identify HBV-associated host co-expression modules. These modules were subsequently characterized in independent liver transcriptomic datasets representing distinct metabolic and histological liver contexts using single-sample gene set enrichment analysis (ssGSEA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MAFLD was independently associated with lower circulating HBV DNA levels. This association varied across MAFLD phenotypes, with the lowest HBV DNA levels observed in overweight- or obesity-related MAFLD. Transcriptomic analyses identified HBV-associated host co-expression programs linked to lipid and cholesterol metabolism, inflammatory signaling, and antiviral responses. Cross-cohort analyses further showed that selected modules varied across distinct metabolic and fibrotic liver contexts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MAFLD is associated with reduced HBV DNA levels in patients with CHB, especially in overweight- or obesity-related MAFLD. The transcriptomic findings provide complementary biological context for this clinical association and highlight metabolic and immune pathways that warrant further mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1926645","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:35:02Z","timestamp":1789533302000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["MAFLD is linked to lower HBV DNA levels in chronic hepatitis B: clinical and transcriptomic insights"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoyun","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Geriatric, The Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/S0140-6736(22)01468-4","article-title":"Hepatitis B","volume":"401","author":"Jeng","year":"2023","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J Hepatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/s41579-024-01121-2","article-title":"Hepatitis B and D virus entry","volume":"23","author":"Watashi","year":"2025","journal-title":"Nat Rev 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