{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:57:26Z","timestamp":1792083446854,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Chronic hepatitis B (CHB) remains a major global health burden. Current therapies rarely achieve a functional cure due to low rates of HBsAg clearance, the persistence of the viral replication template\u2014covalently closed circular DNA (cccDNA)\u2014and the need for lifelong treatment. GST\u2010HG131 is a first\u2010in\u2010class, orally bioavailable small\u2010molecule inhibitor of PAPD5\/7, key host factors involved in HBV mRNA stabilization and HBsAg production. We evaluated the safety, tolerability and antiviral activity of GST\u2010HG131 in patients with CHB receiving nucleos(t)ide analogue (NUC) therapy in a randomized, double\u2010blind, placebo\u2010controlled Phase IIa study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This double\u2010blind, randomized, placebo\u2010controlled Phase IIa study evaluated the efficacy and safety of GST\u2010HG131 in 45 CHB patients. Cohorts 1 and 2 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910 each; 8 active, 2 placebo) received 30\u2009mg or 60\u2009mg BID for 28\u2009days, respectively. Cohort 3 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200925; 20 active, five placebo) received 30\u2009mg BID for 12\u2009weeks. All participants were on nucleos(t)ide analog monotherapy for more than 6\u2009months, with HBsAg between 100 and 1500\u2009IU\/mL, and serum ALT below 1\u00d7 ULN.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At Day 28, HBsAg reductions were \u22120.65 log\n                      <jats:sub>10<\/jats:sub>\n                      IU\/mL in the 30\u2009mg BID 28\u2010day group and \u22120.53 log\n                      <jats:sub>10<\/jats:sub>\n                      IU\/mL in the 60\u2009mg BID 28\u2010day group. The 30\u2009mg BID 12\u2010week group showed a greater reduction of \u22120.89 log\n                      <jats:sub>10<\/jats:sub>\n                      IU\/mL at the end of treatment versus placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Two\u2010thirds of treated patients achieved a\u2009&gt;\u200950% reduction in HBsAg with a maximum decrease of 1.64 log\n                      <jats:sub>10<\/jats:sub>\n                      IU\/mL. Notably, 76.5% of patients in the 12\u2010week group achieved HBsAg below 100\u2009IU\/mL. Rebounds in HBsAg were observed following treatment discontinuation. GST\u2010HG131 was well tolerated, with no dose\u2010related toxicity or emerging safety concerns across all cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GST\u2010HG131, a first\u2010in\u2010class oral PAPD5\/7 inhibitor, demonstrated favourable safety and significant HBsAg reduction in patients with CHB. The greatest antiviral activity was observed after 12\u2009weeks of treatment, supporting further clinical development of GST\u2010HG131 as a component of functional cure strategies for CHB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT06263959\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70918","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:06:16Z","timestamp":1791871576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, Tolerability and Antiviral Activity of\n                    <scp>GST<\/scp>\n                    \u2010\n                    <scp>HG131<\/scp>\n                    in Chronic Hepatitis B: A Randomized, Double\u2010Blind Phase\n                    <scp>IIa<\/scp>\n                    Study"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3149-8422","authenticated-orcid":false,"given":"Yuming","family":"Guo","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Xu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5724-3464","authenticated-orcid":false,"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Mao","sequence":"additional","affiliation":[{"name":"Fujian Akeylink Biotechnology Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Akeylink Biotechnology Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-8115","authenticated-orcid":false,"given":"Fanping","family":"Meng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8318-6888","authenticated-orcid":false,"given":"Junliang","family":"Fu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8214-462X","authenticated-orcid":false,"given":"Dong","family":"Ji","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Ji","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqian","family":"Cheng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-6748","authenticated-orcid":false,"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-9206","authenticated-orcid":false,"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0994-0384","authenticated-orcid":false,"given":"Zuxiong","family":"Huang","sequence":"additional","affiliation":[{"name":"Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3269-8549","authenticated-orcid":false,"given":"Dachuan","family":"Cai","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Fujian Akeylink Biotechnology Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Yan","sequence":"additional","affiliation":[{"name":"Fujian Akeylink Biotechnology Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Yan","sequence":"additional","affiliation":[{"name":"Fujian Akeylink Biotechnology Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Akeylink Biotechnology Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8230-8583","authenticated-orcid":false,"given":"Jinlin","family":"Hou","sequence":"additional","affiliation":[{"name":"Nanfang Hospital Nanfang Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5437-6028","authenticated-orcid":false,"given":"George","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Akeylink Biotechnology Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-6685","authenticated-orcid":false,"given":"Fu\u2010Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"1257","article-title":"Application of Interferon Response\u2010Related Gene Array to the Antiviral Treatment Outcome in Chronic Hepatitis C","volume":"57","author":"Xing T. 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M.","year":"2022","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-020-10098-y"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18131"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2022.128977"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14801"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.01.007"},{"key":"e_1_2_13_19_1","first-page":"673","article-title":"Quantitative Hepatitis B Core Antibody Levels Can Be Used as a Predictive Index of HBsAg Clearance","volume":"29","author":"Lin X.","year":"2021","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104995"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2021.06.004"},{"key":"e_1_2_13_22_1","first-page":"580","article-title":"Clinical Analysis of Four Cases of HBsAg Seroconversion in Patients With HBeAg\u2010Positive Chronic Hepatitis B After Receiving Interferon Alpha Therapy","volume":"29","author":"Wu F. P.","year":"2021","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2021.101723"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14897"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa462"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0037-0"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2798"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210027"},{"key":"e_1_2_13_29_1","article-title":"Current Status and Challenges of Therapeutic Targets, Novel Drugs and Delivery Systems for Hepatitis B Virus Infection","volume":"15","author":"Mak L. 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