{
  "abstract": "Background Bulevirtide represents the first authorized entry inhibitor indicated for the management of chronic hepatitis D (CHD), exerting its antiviral activity by blocking the sodium taurocholate co-transporting polypeptide (NTCP). Although clinical results have been promising, marked variability among patients in drug exposure and therapeutic effectiveness has been reported. So far, limited evidence has explored the variability in bulevirtide plasma concentrations and the potential role of genetic polymorphisms. The present study sought to evaluate bulevirtide plasma levels, along with biochemical and virological markers at different time points, and to investigate the impact of NTCP gene variants on clinical outcomes, taking into account virological and biochemical responses at week (W) 60.Material and Methods patients with CHD treated with bulevirtide were included in the study. Bulevirtide plasma levels, together with biochemical and virological markers, were measured at baseline and at weeks (W) 4/12/24/36/48 and 60 using liquid chromatography-mass spectrometry. The pharmacogenetic evaluation targeted NTCP genetic variants (rs8011311-rs2296651), analyzed through PCR genotyping.Results Seventeen patients were initially recruited; five were later excluded due to incomplete follow-up and inadequate adherence to therapy. Among the twelve patients included in the final analysis, 75% were male. Median age was 51.5 years and median BMI was 24.5 kg/m 2; cirrhosis was present in 50% of cases. At baseline, median ALT level was 80.5 IU/L and median HDV RNA was 5.3 Log. Liver stiffness significantly decreased at week 48 compared with baseline (p=0.041, figure 1). Lipid parameters were not affected by treatment, while a slight, non-significant increase in bile acids was observed. No adverse events were reported.At week 60, virological response was achieved in 4 patients (33.3%), biochemical response in 4 (33.3%), and a combined response in 3 (25%).Median plasma bulevirtide concentration was 0.4 ng/mL (IQR 0.3–0.5) at W4, 0.9 ng/mL (IQR 0.4–1.9) at W12, 0.6 ng/mL (IQR 0.3–1.6) at W24, 1.0 ng/mL (IQR 0.5–1.3) at W36, 1.2 ng/mL (IQR 0.5–7.2) at W48, and 0.7 ng/mL (IQR 0.3–2.1) at W60. Concomitant medications did not appear to influence bulevirtide exposure, whereas liver stiffness values >12 kPa were associated with differences in drug levels, particularly at week 12 (p=0.026).Regarding pharmacogenetic findings, patients carrying the NTCP rs8011311 GC/CC genotype exhibited lower bulevirtide concentrations compared with those with the GG genotype at week 4 (p=0.047).Conclusions This exploratory study is the first to describe bulevirtide plasma concentrations in patients undergoing 60 weeks of treatment and to investigate the influence of genetic factors, although sample size was limited. Larger-scale studies are needed to support the development of individualized dosing approaches aimed at optimizing efficacy and safety in patients with HDV infection.Abstract P168 Figure 1Stiffness levels during the different weeks",
  "authors": [
    {
      "affiliations": [
        "University of Turin, Turin, Italy"
      ],
      "name": "J Cusato"
    },
    {
      "affiliations": [
        "Amedeo di Savoia Hospital, Turin, Italy"
      ],
      "name": "M Antonucci"
    },
    {
      "affiliations": [
        "University of Turin, Turin, Italy"
      ],
      "name": "A Palermiti"
    },
    {
      "affiliations": [
        "University of Turin, Turin, Italy"
      ],
      "name": "A Manca"
    },
    {
      "affiliations": [
        "Amedeo di Savoia Hospital, Turin, Italy"
      ],
      "name": "S Perosino"
    },
    {
      "affiliations": [
        "Amedeo di Savoia Hospital, Turin, Italy"
      ],
      "name": "F Onelia"
    },
    {
      "affiliations": [
        "University of Turin, Turin, Italy"
      ],
      "name": "A De Nicolò"
    },
    {
      "affiliations": [
        "Amedeo di Savoia Hospital, Turin, Italy"
      ],
      "name": "C Quarta"
    },
    {
      "affiliations": [
        "University of Turin, Turin, Italy"
      ],
      "name": "A D’Avolio"
    },
    {
      "affiliations": [
        "Amedeo di Savoia Hospital, Turin, Italy"
      ],
      "name": "S Bonora"
    },
    {
      "affiliations": [
        "Amedeo di Savoia Hospital, Turin, Italy"
      ],
      "name": "G Di Perri"
    },
    {
      "affiliations": [
        "Amedeo di Savoia Hospital, Turin, Italy"
      ],
      "name": "L Marinaro"
    }
  ],
  "title": "P168 Comprehensive pharmacogenetic, pharmacokinetic and clinical assessment of bulevirtide in chronic hepatitis D patients",
  "uid": "4656f79e-666c-569c-9ca1-1f00c8bfc79d"
}