{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T12:11:27Z","timestamp":1793621487202,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We studied whether 48\u2009weeks of PEG\u2010IFN alfa\u20102a add\u2010on increases HBsAg\u2010decline and clearance in HBeAg\u2010negative patients on long\u2010term nucleo(s)tide analogue (NA) therapy. In this investigator\u2010initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg\u2010negative patients treated with NA\u2009&gt;\u200912\u2009months, with HBVDNA\u2009&lt;\u2009200\u2009IU\/mL, were enrolled. Patients were randomized 2:1 to 48\u2009weeks of PEG\u2010IFN alfa\u20102a add\u2010on (180\u2009\u03bcg per week) or continued NA\u2010monotherapy with subsequent follow\u2010up to Week 72. Endpoints were HBsAg decline (\u22651\u2009log<jats:sub>10<\/jats:sub> IU\/mL) and HBsAg clearance at Week 48. Of the 86 patients in the modified\u2010intention\u2010to\u2010treat analysis, 58 patients received PEG\u2010IFN add\u2010on, and 28 continued NA monotherapy. At Week 48, 16(28%) patients achieved HBsAg decline \u22651\u2009log<jats:sub>10<\/jats:sub> in the add\u2010on arm versus none on NA\u2010monotherapy (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), and HBsAg clearance was observed in 6 (10%) PEG\u2010IFN add\u2010on patients versus 0% NA\u2010monotherapy (<jats:italic>p<\/jats:italic>\u2009=\u2009.01). HBVRNA was only detected in 2% after PEG\u2010IFN treatment versus 19% in NA\u2010monotherapy (<jats:italic>p<\/jats:italic>\u2009=\u2009.002) at Week 48. PEG\u2010IFN add\u2010on therapy was well tolerated in majority of patients. Low baseline HBsAg levels (&lt;10\u2009IU\/mL) identified patients most likely to achieve HBsAg loss with PEG\u2010IFN add\u2010on, whereas an HBsAg level\u2009&gt;\u2009200\u2009IU\/mL at on\u2010treatment Week 12 was highly predictive of non\u2010response (NPV\u2009=\u2009100%). Addition of PEG\u2010IFN to long\u2010term NA enhanced HBsAg decline and increased the chance of HBsAg clearance in HBeAg\u2010negative patients on long\u2010term NA. On\u2010treatment HBsAg levels &gt;200\u2009IU\/mL identify patients unlikely to benefit from PEG\u2010IFN add\u2010on and could be used as a potential stopping\u2010rule for PEG\u2010IFN therapy. Our findings support further exploration of immune modulation add\u2010on to antiviral therapy, preferably using response\u2010guided strategies, to increase functional cure rates in patients with CHB.<\/jats:p>","DOI":"10.1111\/jvh.13918","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T04:11:10Z","timestamp":1705723870000},"page":"197-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Addition of PEG\u2010interferon to long\u2010term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg\u2010negative chronic hepatitis B"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1579-1680","authenticated-orcid":false,"given":"Mina S.","family":"Farag","sequence":"first","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-4920","authenticated-orcid":false,"given":"Margo J. 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