{
  "abstract": "Background Exhausted CD8+T cells contribute to viral persistence and chronic hepatitis B (CHB). Despite their significance, there is still a lack of comprehensive understanding of exhausted CD8+T cells in patients with functional cure of CHB.Methods Single-cell RNA sequencing (scRNA-seq) data were obtained from liver samples of 22 individuals: 11 treatment-naïve CHB patients, 4 peg-IFN ± NUC-treated patients without HBsAg loss, and 7 peg-IFN ± NUC-treated patients with HBsAg loss (BioProject PRJNA1096305; Study SRP499879). Gene expression and clinical data from liver biopsies of 124 CHB patients were retrieved from GSE84044. Comprehensive scRNA-seq analysis, including quality control, dimensionality reduction, clustering, cell type annotation, and pseudotime trajectory reconstruction, was performed.Results Significantly reduced hepatic exhausted CD8+T cells were observed in patients with HBsAg loss compared to those without HBsAg loss and treatment-naïve CHB patients ( IDDF2026-ABS-0371 Figure 1). Pseudotime trajectory analysis indicated that exhausted CD8+ T cells represented a terminally differentiated T-cell subset (IDDF2026-ABS-0371 Figure 2). Exhausted CD8+ T cells from patients who achieved HBsAg loss expressed lower levels of inhibitory receptors, including CTLA4, LAG3, PDCD1, HAVCR2, TIGIT, and LYAN, relative to patients without HBsAg loss and treatment-naïve individuals (IDDF2026-ABS-0371 Figure 3). Moreover, these cells exhibited enhanced cytotoxicity, characterized by elevated expression of GZMA, GZMH, GZMK, IFNG, CST7, NKG7 (IDDF2026-ABS-0371 Figure 4). Transcription factor (TF) analysis identified IRF4 as specifically expressed in exhausted CD8+T cells, showing a positive correlation with the aforementioned inhibitory receptors. IRF4 expression was also significantly lower in patients with HBsAg loss than in those without HBsAg loss and treatment-naïve CHB patients (IDDF2026-ABS-0371 Figure 5). External clinical samples further validated that hepatic IRF4 expression was significantly elevated in CHB patients compared to normal controls and was associated with clinical parameters, including AST, HBV DNA, Scheuer grade, and stage. In addition, hepatic IRF4 expression correlated significantly with the inhibitory receptors (IDDF2026-ABS-0371 Figures 6).Conclusions Lower percent of exhausted CD8+T cells with less inhibitory receptors and enhanced cytotoxicity may contribute to functional cure in CHB patients treated with peg-IFN. IRF4 may serve as a key regulator of T cell exhaustion and a potential therapeutic target and predictive biomarker for functional cure in chronic hepatitis B.Abstract IDDF2026-ABS-0371 Figure 1Abstract IDDF2026-ABS-0371 Figure 2Abstract IDDF2026-ABS-0371 Figure 3Abstract IDDF2026-ABS-0371 Figure 4Abstract IDDF2026-ABS-0371 Figure 5Abstract IDDF2026-ABS-0371 Figure 6",
  "authors": [
    {
      "affiliations": [
        "Guangzhou First People’s Hospital, South China University of Technology, China"
      ],
      "name": "Gang Ning"
    },
    {
      "affiliations": [
        "Guangzhou First People’s Hospital, South China University of Technology, China"
      ],
      "name": "Shuzhen Chen"
    },
    {
      "affiliations": [
        "The First People’s Hospital of Foshan, China"
      ],
      "name": "Xianxiang Liao"
    },
    {
      "affiliations": [
        "The First People’s Hospital of Foshan, China"
      ],
      "name": "Hongye Jiang"
    }
  ],
  "title": "IDDF2026-ABS-0371 Integrated single-cell transcriptomics and bulk transcriptomics identify reduced exhausted CD8+T with less inhibitory receptors and enhanced cytotoxicity contribute to functional cure in chb patients treated with peg-IFN",
  "uid": "81118c04-592e-5d18-998b-3ea1e043b463"
}