{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:04:54Z","timestamp":1790679894453,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T00:00:00Z","timestamp":1598745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Innovative Research Team"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81721002"],"award-info":[{"award-number":["81721002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2018ZX10301202"],"award-info":[{"award-number":["2018ZX10301202"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The mechanisms underlying B-cell hyperactivation in patients with chronic hepatitis B virus (HBV) infection remain largely undefined. The present study assessed the clinical characteristics of the CD39\/CD73\/adenosine pathway in patients with chronic hepatitis B (CHB).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We examined CD39 and CD73 expression and adenosine production by B-cells from 202 HBV-infected patients. B-cell-activation phenotypes were assessed by flow cytometry after CpG+CD40 ligand stimulation with or without blockade and activation of the adenosine pathway.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CD39 and CD73 expression on circulating B-cells was decreased in CHB patients with high HBV DNA, HBeAg positivity, high HBsAg levels, and active liver inflammation, and was hierarchically restored in complete responders according to HBeAg seroconversion or HBsAg reduction. However, CD39 and CD73 expression on activated memory and tissue-like memory B-cell subsets in complete responders was not increased despite effective antiviral treatments. Furthermore, CD39 and CD73 expression on intra-hepatic B-cells was decreased in inflammatory livers. In vitro, B-cells from CHB patients showed a markedly reduced capacity to generate CD39\/CD73-dependent extracellular adenosine and expressed increased levels of activation markers after adenosine-production blockade. Contrastingly, metformin significantly reduced activation-marker expression via regulating AMP-activated protein kinase.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The skewed CD39 and CD73 expression on B-cells was associated with a high viral burden, liver inflammation, and antiviral efficacy in CHB patients, and the skewed CD39\/CD73\/adenosine pathway contributed to B-cell hyperactivation. Regulation of the CD39\/CD73\/adenosine pathway using metformin may represent a therapeutic option to reverse HBV-induced immune pathogenesis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/gastro\/goaa048","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T19:11:37Z","timestamp":1594062697000},"page":"49-58","source":"Crossref","is-referenced-by-count":28,"title":["Skewed CD39\/CD73\/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B"],"prefix":"10.1093","volume":"9","author":[{"given":"Shuang-Nan","family":"Zhou","sequence":"first","affiliation":[{"name":"Medical School of Chinese PLA, Beijing, P. R. China"},{"name":"Infectious Disease Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, P. R. China"},{"name":"Liver transplatation Center, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrated TCM & Western Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"International Center for Liver Disease Treatment, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xia","sequence":"additional","affiliation":[{"name":"Infectious Disease Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, P. R. 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