{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:22:20Z","timestamp":1791829340225,"version":"4.3.4"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jtim-2026-0018_s_011\">\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>The treatment options for hepatitis B surface antigen (HBsAg) clearance are limited for patients who have failed pegylated interferon-\u03b1 (Peg-IFN\u03b1) therapy. Given preclinical evidence that PD-1 blockade boosts antiviral immunity, this study aims to evaluate the efficacy and safety of PD-1 inhibitors in chronic hepatitis B (CHB) patients who have failed interferon therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jtim-2026-0018_s_012\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This non-randomized controlled trial was conducted in CHB patients who failed to achieve HBsAg clearance after 48 weeks of Peg-IFN\u03b1 therapy. Including two groups: (i) a PD-1 inhibitor plus Peg-IFN\u03b1 group receiving sintilimab 1 mg\/kg\/12 weeks plus Peg-IFN\u03b1 180 \u03bcg\/week (\n                      <jats:italic>n<\/jats:italic>\n                      = 33) or (ii) a Peg-IFN\u03b1 group continuing Peg-IFN\u03b1 therapy (\n                      <jats:italic>n<\/jats:italic>\n                      = 31). The primary endpoint was HBsAg clearance at week 24.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jtim-2026-0018_s_013\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The PD-1 inhibitor plus Peg-IFN\u03b1 group included 33 patients and the Peg-IFN\u03b1 group included 31 patients. At week 24, HBsAg clearance occurred in 30.3% of PD-1 inhibitor plus Peg-IFN\u03b1 group\n                      <jats:italic>versus<\/jats:italic>\n                      9.7% of Peg-IFN\u03b1 group (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.047). Median HBsAg declined by \u20130.916 log\n                      <jats:sub>10<\/jats:sub>\n                      IU\/mL in the PD-1 inhibitor plus Peg-IFN\u03b1 group compared with \u20130.067 log\n                      <jats:sub>10<\/jats:sub>\n                      IU\/mL in Peg-IFN\u03b1 group (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.013). In the PD-1 inhibitor plus Peg-IFN\u03b1 group, alanine transaminase (ALT) rose transiently at week 12 only among patients who ultimately cleared HBsAg. Sintilimab increased stomatitis (12.1%) and recurrent fever (36.4%), but the frequency of grade \u2265 3 adverse events did not differ from Peg-IFN\u03b1 group. Enzyme-linked immunosorbent assay (ELISA) profiling showed progressive induction of ISG15 after sintilimab, and patients achieving HBsAg clearance displayed higher baseline and week-12 OAS1 concentrations than non-clearers (both\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jtim-2026-0018_s_014\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Quarterly sintilimab add-on therapy triples the short-term HBsAg clearance rate in interferon-refractory CHB without major additional toxicity. A week-12 ALT surge and elevated OAS1 may serve as early biomarkers of response, but confirmation in larger randomized trials is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jtim-2026-0018","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T10:16:23Z","timestamp":1771323383000},"page":"123-133","source":"Crossref","is-referenced-by-count":3,"title":["Add-on PD-1 inhibitor with Peg-IFN\u03b1 therapy favors functional cure of chronic hepatitis B patients"],"prefix":"10.1515","volume":"14","author":[{"given":"Yaping","family":"Li","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenrui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"He","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoe","family":"Gou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases , 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":"Senior Department of Infectious Diseases, Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-5711","authenticated-orcid":false,"given":"Shuangsuo","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"2026021906293002296_j_jtim-2026-0018_ref_001","doi-asserted-by":"crossref","unstructured":"Terrault NA, Bzowej NH, Chang K-M, Hwang JP, Jonas MM, Murad MH. 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