{
  "abstract": "Background Chronic Hepatitis Delta (HDV) is the most severe form of viral hepatitis. The entry inhibitor bulevirtide (BLV) was recently approved for treatment, but validated predictors of treatment response remain limited. HDV replication induces intense activation of innate immunity, with elevated cytokine production and liver inflammation. This study aimed to analyze the inflammatory and pro-fibrotic cytokine profiles of HBV-HDV coinfected patients to identify potential predictors of response to BLV therapy.Material and Methods Twenty-six patients with chronic HBV-HDV hepatitis treated with BLV were consecutively enrolled (April 2022 - May 2024). Biochemical, virological and immunological parameters were evaluated at baseline (T0) and at weeks 4, 12, 24, and 48. Plasma concentrations of IL-6, IL-8, TNF-α, CXCL10 and IFN-γ were quantified using the automated Simple Plex platform. Other parameters included quantification of HBsAg and anti-HBc IgG. A combined BLV treatment response was defined as the concomitant achievement of HDV-RNA suppression (≥2 log10 reduction from baseline) and ALT normalization at week 48. Statistical analysis included Principal Component Analysis (PCA) and univariable logistic regression.Results Among 26 participants, the median age was 50 years [IQR 47-59], 14 (54%) were female, and 19 (73%) originated from Eastern Europe. Overall, 17 (65%) had compensated cirrhosis, including 4 with esophageal and/or gastric varices (13 Child A5 and 4 Child A6). One patient had a history of resected hepatocellular carcinoma (HCC). At T0 median AST and ALT levels were 72 U/L [48-106] and 88 U/L [56-113], respectively; HDV-RNA was 4.83 log10 cp/mL [3.46-5.76]. After 48 weeks of BLV therapy, 13 (50%) patients achieved a combined response. In univariable analyses, factors associated with a combined response included higher baseline CXCL10 levels (OR 1.12 per 10-unit increase, p=0.019) and lower baseline anti-HBc IgG levels (OR 0.88 per 10-unit increase, p = 0.007) ( table 1).PCA showed that baseline levels of CXCL10, anti-HBc, and IFN-γ were the main characteristics that differentiated responders from non-responders, supporting a distinct immunological profile among responders.Conclusions These preliminary findings identify baseline CXCL10 as a potential predictor of response to BLV. therapy. Elevated baseline CXCL10 levels characterize a subgroup of patients with an activated interferon-driven immune profile, which may be associated with a higher likelihood of treatment response. Further studies are warranted to validate CXCL10 as a non-invasive biomarker to support personalized therapeutic approaches in chronic HDV.Abstract P99 Table 1Baseline (T0) characteristics associated with a combined week-48 response to BLV",
  "authors": [
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "C Taibi"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "E Cimini"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "G Grassi"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "A Caioli"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "A Rianda"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "F Cristofanelli"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "S Pauciullo"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "V Zulian"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "AR Garbuglia"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "AM Geretti"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "E Biliotti"
    },
    {
      "affiliations": [
        "National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy"
      ],
      "name": "G D’Offizi"
    }
  ],
  "title": "P99 Immunological predictive factors for treatment response during bulevirtide therapy in HBV-HDV coinfected patients",
  "uid": "1ebe67d7-cd6c-5cbb-8591-ccff2dcb8bb3"
}