{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:11:31Z","timestamp":1780596691121,"version":"3.54.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"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:sec><jats:title>Background and Aims<\/jats:title><jats:p>We previously showed that overt acute hepatitis B (AHB) was more severe in female patients. Using the same cohort and AHB mouse model, we examined the underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Baseline biochemistry, virological and cytokine assays, and T helper (Th)1 and Th2 immune markers of 118 consecutive patients were analyzed. The decompensated livers of AHB and chronic hepatitis B (CHB) patients who underwent liver transplantation were analyzed immunohistochemically. B6 mice were hydrodynamically injected with pHBV1.3 plasmids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Decompensated AHB patients (n=41) were older, more often female, and had higher alanine aminotransferase (ALT), soluble programmed cell death protein 1 (sPD-1) levels, and neutrophil-lymphocyte ratios but lower rates of HBeAg positivity and quantitative HBsAg, interferon (IFN)-\u03b3-inducible protein 10 (IP-10), IFN-\u03b3, and interleukin-4 (IL-4) levels than the compensated patients. Female sex (95% CI OR=1.07~54.9), age (1.06~1.40), and ALT levels (1.001~1.004) were associated with hepatic decompensation. Higher sPD-1 but lower IFN-\u03b3 and IL-4 levels were observed in female patients. Compared to CHB, decompensated AHB livers had more IL-17-positive cells but fewer HBsAg-positive cells and lower CD4\/CD8 ratios. Higher serum IL-17 levels were noted in the female AHB mice than those in the males.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Females predominated in decompensated AHB, in which downregulated IFN-\u03b3 and IL-4 with augmented hepatic IL-17-positive cell development indicated accelerating destructive immunity to enhance viral clearance. The early surge of serum IL-17 was confirmed in the female AHB mice. Targeting the pathway involving IFN-\u03b3, IL-4, and IL-17 might prevent liver transplantation or fatality in decompensated AHB.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.631976","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T05:06:06Z","timestamp":1636607166000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 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