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We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side\u00a0analogue-treated patients who achieved HBsAg loss with peg-interferon-\u03b1(peg-IFN-\u03b1) add-on or switch treatment in a randomised clinical trial. Cytokines\/chemokines from plasma were compared between those with\/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-\u03b1 treatment\u00a0resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings\u00a0show that\u00a0more than one immune pathway to HBsAg loss was found with peg-IFN-\u03b1 therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.<\/jats:p>","DOI":"10.1038\/s41598-021-86836-5","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T10:03:08Z","timestamp":1617357788000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment"],"prefix":"10.1038","volume":"11","author":[{"given":"Sriram","family":"Narayanan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veonice Bijin","family":"Au","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Khakpoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Ahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivashini","family":"Kaliaperumal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernett","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen Wei","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Tay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seng Gee","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"86836_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.poly.2012.11.010","volume-title":"Global Hepatitis Report, 2017","author":"Geneva: World Health Organization","year":"2017","unstructured":"Geneva: World Health Organization. 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