{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T18:25:02Z","timestamp":1780424702189,"version":"3.54.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Understanding the natural history of hepatitis B virus (HBV) infection helps determine the optimal timing of antiviral therapy. However, a gap exists in the literature regarding the dynamics of the natural history of HBV infection in pregnant women with chronic hepatitis B (CHB). This study aimed to explore the natural history of HBV infection during pregnancy and the postpartum period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective\u2013prospective real-world study involving 276 pregnant women with CHB. Infection dynamics during pregnancy were characterized in 228 hepatitis B e-antigen (HBeAg)-positive and 48 HBeAg-negative participants, respectively, and during postpartum follow-up in 108 HBeAg-positive and 21 HBeAg-negative participants. HBeAg-positive participants received short-term antiviral intervention according to current guidelines. Liver disease progression was also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Throughout pregnancy, the proportion of patients in the immune tolerance (IT) phase increased progressively, whereas the proportions of patients in the HBeAg-positive indeterminate phase (IP) and HBeAg-positive immune-active (IA) phase decreased. In the third trimester, the IT phase was dominant (48.7%), followed by the HBeAg-positive IP phase (24.6%), the HBeAg-positive IA phase (9.4%), the inactive carrier (IC) phase (9.4%), the HBeAg-negative IP phase (7.1%), and the HBeAg-negative IA phase (0.9%). During the postpartum period, a numerically higher cumulative incidence of phase maintenance (p = 0.150) and a significantly lower cumulative incidence of transition to the HBeAg-positive IA phase (p &amp;lt; 0.001) were observed in pregnant women in the IT phase compared with those in the HBeAg-negative IP phase. The cumulative incidence of phase maintenance (p = 0.900) and transition to the HBeAg-negative IA phase (p = 0.560) were comparable between pregnant women in the IC phase and those in the HBeAg-negative IP phase. The risk of postpartum liver disease progression was low among pregnant women across all disease phases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pregnancy may have a pronounced impact on the dynamics of HBV infection in HBeAg-positive patients, particularly those in the IP phase at 24\u201328 weeks of gestation. Close postpartum monitoring is therefore warranted for this specific population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:related-object>\n                      <jats:ext-link>https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      , identifier ChiCTR2100054116.\n                    <\/jats:related-object>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1652690","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:58:55Z","timestamp":1767769135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Higher risk of postpartum phase transition to immune-active among HBeAg-positive pregnant women with indeterminate phase"],"prefix":"10.3389","volume":"15","author":[{"given":"Qiao","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Qing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ling","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.cgh.2007.01.005","article-title":"Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome","volume":"5","author":"Andreani","year":"2007","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/1751-2980.12854","article-title":"Consensus on the diagnosis and treatment of hepatic fibrosis (2019)","volume":"21","year":"2020","journal-title":"J. Digest Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.jhep.2024.11.018","article-title":"Histological severity, clinical outcomes and impact of antiviral treatment in indeterminate phase of chronic hepatitis B: a systematic review and meta-analysis","volume":"82","author":"Che-To Lai","year":"2024","journal-title":"J. Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1136\/gutjnl-2014-308211","article-title":"Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B","volume":"64","author":"Giles","year":"2015","journal-title":"Gut"},{"key":"B5","unstructured":""},{"key":"B6","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1016\/j.cgh.2021.01.019","article-title":"Natural history and hepatocellular carcinoma risk in untreated chronic hepatitis B patients with indeterminate phase","volume":"20","author":"Huang","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B7","volume-title":"IBM SPSS statistics for macintosh (Version 24.0)","year":"2016"},{"key":"B8","doi-asserted-by":"publisher","first-page":"8","DOI":"10.4103\/tjem.tjem_198_23","article-title":"Unraveling the clinical significance and prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and delta neutrophil index: An extensive literature review","volume":"24","author":"Islam","year":"2024","journal-title":"Turk J. Emergency Med."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12707","article-title":"Peripartum cytokine flares in a multiethnic cohort of chronic hepatitis B carriers does not correlate with hepatitis B virus suppression or increased risk of liver disease","volume":"78","author":"Joshi","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","author":"Lampertico","year":"2017","journal-title":"J. Hepatol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13083","article-title":"Chronic hepatitis B infection alters peripheral immune response in women with reproductive failure","volume":"81","author":"Li","year":"2019","journal-title":"Am. J. Reprod. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1111\/j.1440-1746.2006.04198.x","article-title":"Hepatitis B post-partum e antigen clearance in hepatitis B carrier mothers: Correlation with viral characteristics","volume":"21","author":"Lin","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1002\/hep4.1938","article-title":"Optimized cutoffs of gamma-glutamyl transpeptidase-to-platelet ratio, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 scoring systems for exclusion of cirrhosis in patients with chronic hepatitis B","volume":"6","author":"Liu","year":"2022","journal-title":"Hepatol. Commun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1016\/S2468-1253(24)00226-7","article-title":"Clinical outcomes of untreated adults living with chronic hepatitis B in The Gambia: an analysis of data from the prospective PROLIFICA cohort study","volume":"9","author":"Ndow","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/goae091","article-title":"Postpartum hepatitis flares in mothers with chronic hepatitis B infection","volume":"12","author":"OuYang","year":"2024","journal-title":"Gastroenterol. Rep. (Oxf)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1111\/apt.16123","article-title":"Real-world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate-treated chronic hepatitis B pregnant patients in North America","volume":"52","author":"Samadi Kochaksaraei","year":"2020","journal-title":"Aliment Pharmacol. Ther."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.881321","article-title":"Clinical features and T cell immune characteristics of postpartum hepatitis flare in pregnant women with HBeAg-positive chronic HBV infection","volume":"13","author":"Song","year":"2022","journal-title":"Front. Immunol."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1511855","article-title":"PgRNA closely correlates to cytokine profile in HBeAg-positive pregnant women undergoing prophylactic antiviral intervention","volume":"15","author":"Tang","year":"2024","journal-title":"Front. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12985-025-02632-x","article-title":"Unexpected HBsAg decrease after nucleoside analogues retreatment among HBeAg positive postpartum women: a pilot study","volume":"22","author":"Tang","year":"2025","journal-title":"Virol. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1055774","article-title":"PgRNA kinetics predict HBsAg reduction in pregnant chronic hepatitis B carriers after treatment cessation","volume":"12","author":"Wang","year":"2022","journal-title":"Front. Cell. Infect Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s12985-025-02871-y","article-title":"Profiles and kinetics of PgRNA and clinical characteristics in pregnant, postpartum, and non-pregnant women with chronic HBV infection","volume":"22","author":"Wang","year":"2025","journal-title":"Virol. J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1111\/apt.17272","article-title":"Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone","volume":"57","author":"Wang","year":"2022","journal-title":"Aliment Pharmacol. Ther."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.746759","article-title":"A nomogram for predicting non-rebound in HBV-infected pregnant women with mother-to-child transmission prevention","volume":"8","author":"Wang","year":"2021","journal-title":"Front. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1002\/hep.29302","article-title":"Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis","volume":"66","author":"Xiao","year":"2017","journal-title":"Hepatology"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/v15051212","article-title":"The impact of the definitions of clinical phases on the profiles of grey-zone patients with chronic hepatitis B virus infection","volume":"15","author":"Xu","year":"2023","journal-title":"Viruses"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2023.00320","article-title":"Guidelines for the prevention and treatment of chronic hepatitis B (version 2022)","author":"You","year":"2023","journal-title":"J. Clin. Trans. Hepatol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"474","DOI":"10.4149\/BLL_2021_078","article-title":"Neutrophil-to-lymphocyte ratio, past, present and future perspectives","volume":"122","author":"Zahorec","year":"2021","journal-title":"Bratisl Lek Listy"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1112234","article-title":"Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection","volume":"13","author":"Zhang","year":"2023","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1652690\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:58:56Z","timestamp":1767769136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1652690\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":29,"alternative-id":["10.3389\/fcimb.2025.1652690"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1652690","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"article-number":"1652690"}}