{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:53:38Z","timestamp":1783133618786,"version":"3.54.6"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV\u2019s exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1414594","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T05:04:30Z","timestamp":1721279070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation"],"prefix":"10.3389","volume":"15","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhou","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0422","article-title":"Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives","volume":"29","author":"Huang","year":"2023","journal-title":"Clin Mol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13271","article-title":"The prevalence of steatohepatitis in chronic hepatitis B patients and its impact on disease severity and treatment response","volume":"37","author":"Charatcharoenwitthaya","year":"2017","journal-title":"Liver Int"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30857","article-title":"Nonalcoholic steatohepatitis is associated with liver-related outcomes and all-cause mortality in chronic hepatitis B","volume":"71","author":"Choi","year":"2020","journal-title":"Hepatology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3350\/cmh.2018.0040","article-title":"Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B","volume":"25","author":"Lee","year":"2019","journal-title":"Clin Mol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.965548","article-title":"NAFLD and HBV interplay - related mechanisms underlying liver disease progression","volume":"13","author":"Tourkochristou","year":"2022","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02604-15","article-title":"Hepatitis B virus X protein induces hepatic steatosis by enhancing the expression of liver fatty acid binding protein","volume":"90","author":"Wu","year":"2015","journal-title":"J Virol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.039","article-title":"Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARgamma","volume":"132","author":"Kim","year":"2007","journal-title":"Gastroenterology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.02.016","article-title":"HBx-induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-kappaB-dependent pathways","volume":"397","author":"Kim","year":"2010","journal-title":"J Mol Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i14.2262","article-title":"Hepatitis B virus induces expression of cholesterol metabolism-related genes via TLR2 in HepG2 cells","volume":"19","author":"Li","year":"2013","journal-title":"World J Gastroenterol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.00049","article-title":"Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus","volume":"13","author":"Yan","year":"2012","journal-title":"Elife"},{"key":"B11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41423-020-00558-8","article-title":"Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities","volume":"18","author":"Wen","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nri3793","article-title":"Cholesterol, inflammation and innate immunity","volume":"15","author":"Tall","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323395","article-title":"Chinese Group on the Study of Severe Hepatitis B (COSSH). 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