{
  "abstract": "Background Chronic hepatitis B (CHB) is a major global cause of liver cancer, and metabolic dysfunction-associated steatotic liver disease (MASLD) increasingly co-exists with CHB, potentially accelerating liver disease progression. The molecular interaction between metabolic dysfunction and hepatitis B virus (HBV) remains incompletely understood. We characterised paired hepatic and peripheral gene expression patterns associated with metabolic dysfunction in HBV to identify pathways and candidate gene targets relevant to disease stratification and therapeutic development.Methods Paired liver biopsy and PBMC samples were obtained from patients with untreated CHB with and without co-existing MASLD (n=20). Bulk RNA sequencing was performed, and differential gene expression analysis was conducted using DESeq2 in R (v4.5.1). Differentially expressed genes were identified and subjected to pathway-level interpretation focusing on metabolic-associated transcriptional programmes.Results Comparative analysis identified a distinct hepatic gene expression profile in CHB-MASLD compared with CHB alone. CHB-MASLD was characterised by relative upregulation of stress-responsive genes implicated in nutrient sensing and inflammatory signalling, including ARRDC4, alongside downregulation of genes central to hepatocyte metabolic homeostasis. These included genes involved in amino acid metabolism (TAT), urea cycle function (ASS1), growth hormone-IGF signalling (IGF1), and lysosomal metabolic regulation (RNF152), which were significant after multiple hypothesis testing (adjusted p < 0.05 and |log2 fold change| > 1). Pathway-level interpretation indicated coordinated alterations across metabolic, nutrient-sensing, and stress-associated transcriptional programmes. Overall, the hepatic transcriptomic profile in CHB-MASLD was consistent with altered metabolic regulation accompanied by relative enrichment of stress and inflammatory signalling pathways.Conclusion Untreated CHB with co-existent MASLD displays a hepatic gene expression profile distinct from CHB alone, marked by coordinated changes in metabolic pathways and relative enrichment of stress-associated and inflammatory transcriptional programmes. These findings support metabolic dysfunction as an important modifier of the hepatic molecular landscape in HBV infection and highlight pathways contributing to disease heterogeneity. Earlier therapeutic intervention in CHB-MASLD may therefore be important to mitigate or rebalance adverse transcriptional programmes.",
  "authors": [
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, The Blizard Institute, Barts and The London Faculty of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Eva Parisi"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, The Blizard Institute, Barts and The London Faculty of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Chanelle Fernandes"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, The Blizard Institute, Barts and The London Faculty of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Jantarika Arora"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, The Blizard Institute, Barts and The London Faculty of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom"
      ],
      "name": "Corinna Pade"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, The Blizard Institute, Barts and The London Faculty of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom",
        "Department of Hepatology, Barts Health NHS Trust, London, United Kingdom"
      ],
      "name": "Apostolos Koffas"
    },
    {
      "affiliations": [
        "Centre for Immunobiology & Infection, The Blizard Institute, Barts and The London Faculty 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, The Blizard Institute, Barts and The London Faculty 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": "P64 Distinct hepatic transcriptional programmes in chronic hepatitis B are reshaped by metabolic dysfunction",
  "uid": "c017caf9-19bf-54d1-b3fb-ef1839b8f2dd"
}