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The primary treatment goal is to achieve a functional cure\u2014defined as the loss of hepatitis B surface antigen (HBsAg) 24\u00a0weeks after the cessation of therapy\u2014which reduces liver inflammation, improves histopathology, and decreases the incidence of end-stage liver disease. However, this goal is rarely achieved with current therapies, especially monotherapies. With a deeper understanding of the HBV lifecycle and its interactions with the host immune system, combination therapy strategies are increasingly demonstrating potential to enhance treatment outcomes for CHB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This article reviews the application of novel drugs in combination therapy, analyzes the suitability of different drug combinations, and evaluates their effects on HBsAg clearance rates and overall cure rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The review identified several promising drugs, such as capsid assembly modulators, entry inhibitors, and RNA interference therapies, which demonstrated greater efficacy in combination therapy, achieving higher HBsAg clearance and enhanced immune responses compared to monotherapies. However, effectiveness varied among patient subgroups, highlighting the need for personalized treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combination therapies involving novel drugs hold promise for improving CHB outcomes, particularly in achieving a functional cure. Further research is required to optimize personalized regimens and to assess their long-term safety and efficacy for broader clinical use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-025-10888-2","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T15:22:43Z","timestamp":1760714563000},"page":"9-18","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Combination therapies for chronic hepatitis B in the era of emerging novel drugs"],"prefix":"10.1007","volume":"20","author":[{"given":"Dandan","family":"Weng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunyan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinya","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guancheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujun","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"10888_CR1","unstructured":"World Health Organization. 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