{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:44Z","timestamp":1786115624959,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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":"\n Background and aims<\/jats:title>\n The interplay between hepatitis B virus (HBV) replication and host immunity remains poorly defined in hepatitis B-related acute-on-chronic liver failure (HBV-ACLF). This study aimed to investigate the dynamic antagonism between serum HBV RNA and cytokine-driven hyperinflammation, and to evaluate their combined prognostic value.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this prospective cohort study (March 2021\u2013December 2022), 133 patients with HBV-ACLF were enrolled. Serum levels of HBV RNA and Th1\/Th2 cytokines (IFN-\u03b3, TNF-\u03b1, IL-4, IL-6, IL-10) were measured. Logistic regression analysis was used to identify independent predictors of 12-week prognosis, and to construct and internally validate prognostic models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Non-survivors (40.6%, 54\/133) exhibited significantly lower HBV RNA levels (2.97 \u00b1 1.22 vs. 4.05 \u00b1 1.30 log\n 10<\/jats:sub>\n copies\/mL,\n p<\/jats:italic>\n &lt;\u00a00.001) but 1.2-fold higher IFN-\u03b3 levels (\n p<\/jats:italic>\n &lt;\u00a00.001) compared to survivors. A strong inverse correlation was observed between HBV RNA and IFN-\u03b3 (r = -0.326,\n p<\/jats:italic>\n &lt;\u00a00.001), suggesting that suppressed viral replication may trigger a Th1-dominant hyperinflammatory state. Multivariate logistic regression identified HBV RNA (AUC\u00a0=\u00a00.730, optimal cutoff = 3.98 log\n 10<\/jats:sub>\n copies\/mL) and IFN-\u03b3 (AUC\u00a0=\u00a00.821, optimal cutoff = 496.23 pg\/mL) as independent predictors of 12-week mortality. A nomogram incorporating these factors demonstrated superior predictive performance (AUC\u00a0=\u00a00.917), outperforming the MELD score and achieving comparable accuracy to the COSSH-ACLF II score.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n HBV RNA and Th1 cytokines form a dynamic prognostic axis in HBV-ACLF. Declining HBV RNA, indicative of viral control, paradoxically heralds a cytokine-driven hyperinflammatory state associated with organ failure. This virus-immunity interplay provides a novel stratification tool to guide early immunomodulatory therapy, challenging the traditional focus on viral load alone.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1861087","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:25:23Z","timestamp":1785990323000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["HBV RNA dynamics and cytokine-driven hyperinflammation: a synergistic prognostic axis in hepatitis B-related acute-on-chronic liver failure"],"prefix":"10.3389","volume":"16","author":[{"given":"Keli","family":"Qian","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Virus Hepatitis and Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Infection Control, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Virus Hepatitis and Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Virus Hepatitis and Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.14309\/ajg.0000000000001595","article-title":"Acute-on-chronic liver failure clinical guidelines","volume":"117","author":"Bajaj","year":"2022","journal-title":"Am. 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