{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:25:01Z","timestamp":1790720701486,"version":"4.1.0"},"reference-count":103,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972686"],"award-info":[{"award-number":["81972686"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104391"],"award-info":[{"award-number":["82104391"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2300603"],"award-info":[{"award-number":["2021YFC2300603"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010029","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tsqn202211360"],"award-info":[{"award-number":["tsqn202211360"]}],"id":[{"id":"10.13039\/501100010029","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022YQ75"],"award-info":[{"award-number":["ZR2022YQ75"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023YQ066"],"award-info":[{"award-number":["ZR2023YQ066"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    HBV is an enveloped DNA virus that exclusively infects hepatocytes of humans and some non\u2010human primates. During its viral life cycle, HBV and its structural components can directly regulate the metabolism of hepatocytes, which may reshape the liver immune microenvironment. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells, well known as cytotoxic T lymphocytes for their antiviral immunity, can undergo metabolic reprogramming during chronic HBV infection. Increasing evidence demonstrates that metabolic reprogramming promotes T\u2010cell exhaustion, which is a hallmark of HBV infection. Additionally, complicated metabolites (e.g., glucose, lipids, amino acids and nucleic acids) secreted from hepatocytes or T\u2010cells contribute to the communication between these two cell types, which may facilitate HBV infection and hinder antiviral immune response. In recent years, supplementation of certain specific metabolic substrates or targeting metabolic enzyme genes has been reported to mitigate HBV replication and induce antiviral immune response, holding promise as effective strategies for curing chronic HBV infection. This review provides a thorough overview of recent advances in the metabolic characteristics of hepatocytes and T\u2010cells during HBV infection, discusses the relationship between CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell exhaustion and metabolic reprogramming, and emphasises the therapeutic potential of metabolic approaches in the HBV clinical landscape.\n                  <\/jats:p>","DOI":"10.1111\/liv.70402","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T10:25:29Z","timestamp":1760696729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolic Reprogramming and\n                    <scp>CD<\/scp>\n                    8\n                    <sup>+<\/sup>\n                    T\u2010Cell Exhaustion During Chronic\n                    <scp>HBV<\/scp>\n                    Infection"],"prefix":"10.1111","volume":"45","author":[{"given":"Haohao","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Mu","sequence":"additional","affiliation":[{"name":"Yantai Center for Food and Drug Control  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Xiao","sequence":"additional","affiliation":[{"name":"People's Hospital of Zhoucun  Zibo Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxin","family":"Huo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajun","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Affiliated Hospital of Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuju","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.06.002"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32314"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.09.019"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.3795"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.06.030"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01097-3"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2024.101412"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.078"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02844-06"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33402"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24249"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121172"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118834109"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41264"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.1.477"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.09.052"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141852"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316644"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.05.038"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1620-6"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.005"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.052"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2018.01.007"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005438"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08421"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20316-8"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.259978"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607837103"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.322"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41089"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01803-8"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02531-x"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030655"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008866"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-015-2421-3"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01593-5"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i14.2262"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.02.068"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M079533"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20427"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6817"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2021.12651"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02363-14"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24430"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.01.001"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-016-0318-8"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-1084-6"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20791"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.07.012"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009722"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00849"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3856"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007690"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.07.038"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2205"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.008"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7692"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.024"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00537-8"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.016"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.843242"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12040287"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22967-7"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-018-0683-y"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2025.101612"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.02.015"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200332R"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02845-4"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105570"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6752"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-328734"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(17)30324-0"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4275"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.02.035"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.08.025"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42634-3"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00587-8"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.11.009"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.040"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444904"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22740"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.08.004"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.011"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21804-1"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-022-10462-0"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI121957"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12250-015-3606-3"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.10.034"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003208"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01636-5"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094637"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102563"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.031"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-023-10490-4"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.003"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00403-3"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0270273"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22519"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31712"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-023-00444-4"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2020.1763302"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00859-y"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70402","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T14:41:52Z","timestamp":1763044912000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":103,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/liv.70402"],"URL":"https:\/\/doi.org\/10.1111\/liv.70402","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"assertion":[{"value":"2025-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70402"}}