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We aimed to investigate whether genetic variations of\n                    <jats:italic>TLR6<\/jats:italic>\n                    are associated with the response to PegIFN\u03b1 treatment. This study included 945 HBeAg\u2010positive CHB patients treated with PegIFN\u03b1 for at least 48 weeks and followed for 24 weeks from two multicenter phase IV trials (Cohort 1,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009238; Cohort 2,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009707). Across the\n                    <jats:italic>TLR6<\/jats:italic>\n                    gene, 13 tag\u2010SNPs were selected. Furthermore, a polygenic score (PGS) was developed by incorporating the newly identified variant of\n                    <jats:italic>TLR6<\/jats:italic>\n                    and two previously reported SNPs (\n                    <jats:italic>CD55<\/jats:italic>\n                    _rs28371597 and\n                    <jats:italic>CXCR4<\/jats:italic>\n                    _rs28367495). Both\n                    <jats:italic>TLR6<\/jats:italic>\n                    tag\u2010SNPs and PGS were tested their associations with treatment efficacy. Among the 13 tag\u2010SNPs,\n                    <jats:italic>TLR6<\/jats:italic>\n                    _rs7696175 (\n                    <jats:italic>C<\/jats:italic>\n                    \u2009&gt;\u2009\n                    <jats:italic>T<\/jats:italic>\n                    ) was identified as the most significantly associated variant with HBsAg decline at week 72 in both cohorts. The T allele of\n                    <jats:italic>TLR6<\/jats:italic>\n                    _rs7696175 was significantly associated with greater HBsAg decline, especially higher rates of decline \u2265\u20091 log\n                    <jats:sub>10<\/jats:sub>\n                    IU\/mL and \u2265\u20092 log\n                    <jats:sub>10<\/jats:sub>\n                    IU\/mL at week 72 (Cohort 1\u2009+\u20092:\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.001 for all associations). Moreover, the PGS integrating\n                    <jats:italic>TLR6<\/jats:italic>\n                    _rs7696175 and two previously reported SNPs significantly improved prediction accuracy for HBsAg decline at week 72 (Cohort 1\u2009+\u20092:\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001 for all comparisons) and outperformed single SNPs. Overall, this study identifies\n                    <jats:italic>TLR6<\/jats:italic>\n                    _rs7696175 as a novel genetic biomarker and demonstrates the superiority of a compact PGS for predicting HBsAg decline in PegIFN\u03b1\u2010treated CHB patients, facilitating personalized treatment for CHB.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70872","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:38:55Z","timestamp":1773394735000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Genetic Variant of\n                    <i>TLR6<\/i>\n                    Predicts HBsAg Decline After Pegylated Interferon\u2010Alpha Treatment in HBeAg\u2010Positive Chronic Hepatitis B"],"prefix":"10.1002","volume":"98","author":[{"given":"Wanting","family":"Zeng","sequence":"first","affiliation":[{"name":"National Key Laboratory of Prevention and Treatment of Multiple Organ Injuries, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Hepatology, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"},{"name":"Department of Pathology, Key Laboratory of Molecular Pathology in Tumors of Guangxi Higher Education Institutions The Affiliated Hospital of Youjiang Medical University for Nationalities Baise Guangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialin","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Simulation Center, Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghe","family":"Liang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Prevention and Treatment of Multiple Organ Injuries, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Hepatology, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Hou","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Prevention and Treatment of Multiple Organ Injuries, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Hepatology, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghua","family":"Pan","sequence":"additional","affiliation":[{"name":"Precision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine University of Science and Technology Macau China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Prevention and Treatment of Multiple Organ Injuries, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Hepatology, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlin","family":"Hou","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Prevention and Treatment of Multiple Organ Injuries, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Hepatology, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-2344","authenticated-orcid":false,"given":"De\u2010Ke","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Prevention and Treatment of Multiple Organ Injuries, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong 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