{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:38:24Z","timestamp":1787701104059,"version":"build-2784847793"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Chronic hepatitis B (CHB) affects 260 million people worldwide. Despite advances in antiviral therapies, functional cure, characterized by sustained loss of hepatitis B surface antigen (HBsAg) and durable viral control after treatment cessation, remains infrequent. The PD-1\/PD-L1 immune checkpoint pathway plays an important role in the exhaustion of hepatitis B virus (HBV)-specific T cells, thereby limiting the immune system\u2019s ability to clear HBV. Blocking the PD-1\/PD-L1 pathway has emerged as a promising strategy to overcome this immune exhaustion to some extent and reinvigorate antiviral T-cell responses in CHB patients. Early clinical trials, particularly among patients who have achieved viral suppression with nucleos(t)ide analogues, have demonstrated that PD-1\/PD-L1 inhibitors can significantly reduce HBsAg levels. Notably, a subset of patients has achieved functional cure, particularly among those with low baseline HBsAg levels. These effects have been further enhanced in combination with pegylated interferon, resulting in a functional cure rate of 30%. While challenges remain, such as optimizing dosing regimens, selecting patients, identifying response predictors and managing immune-related adverse events, these findings emphasize the potential of combination regimens involving PD-1\/PD-L1 blockade as a means of achieving a functional cure in CHB patients. Future large-scale randomized controlled trials are essential to fully assess the approach\u2019s efficacy and safety, and to refine its clinical application.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1831739","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:34:19Z","timestamp":1783575259000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["PD-1\/PD-L1 blockade as part of combination strategies toward functional cure of chronic hepatitis B"],"prefix":"10.3389","volume":"17","author":[{"given":"Mei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital 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