{
  "abstract": "Background Single-cell RNA sequencing (scRNA-seq) is increasingly applied to chronic hepatitis B (CHB) cohorts to characterise immune dysfunction and identify pathways relevant to hepatitis B virus (HBV) cure. Although many core aspects of HBV immunopathology were recognised before scRNA-seq, it has enabled higher-resolution characterisation of intrahepatic immune states and interactions; but its incremental translational contribution to cure-directed advances in CHB warrants critical evaluation.Methods MEDLINE was searched via PubMed using a predefined strategy identifying human studies applying scRNA-seq to CHB. Of 221 records identified, 42 underwent full-text review, with 26 included. Data were extracted using a structured proforma, including sequencing platform, tissue source, immune populations analysed, disease phase, treatment status, and links to HBV cure.Results Twenty-six studies applied scRNA-seq to CHB, predominantly using microfluidic droplet-based platforms, with sampling from blood and intrahepatic tissue. Capture of neutrophils, myeloid derived and liver parenchymal cells were limited due to dissociation protocols and cell fragility. Although innate populations were studied less frequently than adaptive cells, scRNA-seq verified innate dysfunction contributes to impaired adaptive immunity. Specific macrophage and NK cell subsets, including FCGR3A + macrophages, were implicated in immunoregulatory and inflammatory pathways, while functional cure was associated with enrichment of immune-active innate populations, including neutrophils, Kupffer cells, and liver-resident NK cells with enhanced effector activity. Adaptive immune findings reinforced existing paradigms of dysfunctional, largely non-HBV-specific liver-resident CD8+ T cells, Treg expansion and impaired B-cell maturation. Recovery-associated populations, including IL-2 linked cytotoxic CD4+ T cells and attenuated HBV polymerase-specific CD8+ T cells, provided mechanistic context for the limited efficacy of checkpoint-based strategies in CHB. Across studies, small sample sizes, heterogeneous cohorts, limited HBV-specific profiling, and infrequent functional validation constrained generalisability.Conclusions In CHB, scRNA-seq refines rather than transforms concepts of immune dysfunction, defining liver-resident immune states and cure-associated innate-adaptive networks, enabling dataset reuse. Progress toward functional cure requires strategic, sustainable application of scRNA-seq with longitudinal sampling and validation to aid HBV cure.",
  "authors": [
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, Blizard Institute, Barts and The London, School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom",
        "Joint first authors"
      ],
      "name": "Akhilesh Mulay"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, Blizard Institute, Barts and The London, School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom",
        "Joint first authors"
      ],
      "name": "James Cai"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, Blizard Institute, Barts and The London, School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Jatarika Arora"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, Blizard Institute, Barts and The London, School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Gerard Hernandez-Mir"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, Blizard Institute, Barts and The London, School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom",
        "Department of Hepatology, Barts Health NHS Trust, London, United Kingdom"
      ],
      "name": "Patrick Kennedy"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, Blizard Institute, Barts and The London, School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom",
        "Department of Hepatology, Barts Health NHS Trust, London, United Kingdom"
      ],
      "name": "Upkar Gill"
    }
  ],
  "title": "P94 Lessons from single-cell transcriptomics in chronic hepatitis B: refinement without redefinition",
  "uid": "62e641e9-c1f2-519c-a16b-70de2752683c"
}