Hepatology communications · 2026
Monocyte-derived IL-1β predicts and promotes HBsAg decline in chronic hepatitis B patients under nucleoside analogue therapy.
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Shigeno Satoshi, Kodama Takahiro, Murai Kazuhiro, Sometani Emi, Yasuda Kentaro, Tahata Yuki, Nishio Akira, Tanaka Satoshi, Miyazaki Masanori, Ohkawa Kazuyoshi, Kakita Naruyasu, Tawara Seiichi, Yakushijin Takayuki, Hikita Hayato, Toyoda Hidenori, Takehara Tetsuo
Аннотация
BACKGROUND: Although nucleos(t)ide analogs (NAs) suppress HBV replication, functional cure-defined by hepatitis B surface antigen (HBsAg) loss-is rarely achieved in chronic hepatitis B (CHB). Immune correlates of HBsAg decline may inform new therapeutic strategies.
METHODS: We profiled peripheral blood mononuclear cells (PBMCs) from NA-treated CHB patients with declining versus sustained HBsAg levels by single-cell RNA sequencing (scRNA-seq), followed by validation in an independent multicenter cohort using transcriptomic and functional assays. In a retrospective cohort, we evaluated serum interleukin-1β (IL-1β) as a predictor of HBsAg decline during long-term follow-up.
RESULTS: scRNA-seq revealed that CD14+CD16- classical monocytes in the HBsAg-declining group expressed significantly higher levels of IL-1β, along with genes involved in antigen presentation and phagocytosis. In the validation cohort, IL-1β expression in circulating CD14+ classical monocytes was also significantly higher in the declining group. Ex vivo stimulation assays demonstrated that recombinant HBsAg induced IL-1β production in monocytes, with stronger responses in the declining group. Recombinant IL-1β suppressed HBsAg secretion from HBV-producing HepG2.2.15 cells in vitro in a dose-dependent manner. In a longitudinal cohort, elevated serum IL-1β predicted subsequent HBsAg decline with an AUROC of 0.71. Multivariate analysis confirmed IL-1β as an independent predictor.
CONCLUSIONS: Monocyte-derived IL-1β is linked to HBsAg decline during NA therapy and may serve as both a predictive biomarker and a potential therapeutic target to achieve functional cure.
METHODS: We profiled peripheral blood mononuclear cells (PBMCs) from NA-treated CHB patients with declining versus sustained HBsAg levels by single-cell RNA sequencing (scRNA-seq), followed by validation in an independent multicenter cohort using transcriptomic and functional assays. In a retrospective cohort, we evaluated serum interleukin-1β (IL-1β) as a predictor of HBsAg decline during long-term follow-up.
RESULTS: scRNA-seq revealed that CD14+CD16- classical monocytes in the HBsAg-declining group expressed significantly higher levels of IL-1β, along with genes involved in antigen presentation and phagocytosis. In the validation cohort, IL-1β expression in circulating CD14+ classical monocytes was also significantly higher in the declining group. Ex vivo stimulation assays demonstrated that recombinant HBsAg induced IL-1β production in monocytes, with stronger responses in the declining group. Recombinant IL-1β suppressed HBsAg secretion from HBV-producing HepG2.2.15 cells in vitro in a dose-dependent manner. In a longitudinal cohort, elevated serum IL-1β predicted subsequent HBsAg decline with an AUROC of 0.71. Multivariate analysis confirmed IL-1β as an independent predictor.
CONCLUSIONS: Monocyte-derived IL-1β is linked to HBsAg decline during NA therapy and may serve as both a predictive biomarker and a potential therapeutic target to achieve functional cure.