{
  "abstract": "Background PD-1 blockade has emerged as a promising approach for functional cure of chronic hepatitis B (CHB).Objective This study aimed to evaluate the safety profile of anti-PD-1 antibody (αPD-1), as well as its impact on hepatitis B surface antigen (HBsAg) and immune responses in a larger cohort of CHB patients.Design In this prospective, open-label study, virally suppressed patients with CHB on nucleos(t)ide analogue (NA) were assigned to receive either 24-week NA monotherapy (n=62) or αPD-1 (half-dose sintilimab) add-on therapy (n=59), with both groups subsequently receiving NA monotherapy for an additional 12-week observation period.Results 93.6% of adverse events (AEs) were grade 1 or 2. Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase were the most common AEs, and they represented the only severe AEs. αPD-1 add-on therapy induced greater HBsAg reductions (mean decline: −0.720 vs −0.034 log 10 IU/mL, p<0.001) and higher HBsAg loss rates (6.1% vs 0%, p=0.166) than NA monotherapy at week 24. Notably, significant HBsAg decline and seroclearance exclusively occurred in the initial 12 weeks of αPD-1 treatment. HBsAg levels did not rebound at 12 weeks after discontinuation of αPD-1 therapy. After αPD-1 therapy, the numbers of HBsAg-specific, HBpol-specific, HBx-specific and HBeAg/HBcAg-specific IFN-γ spots all increased (p<0.05), while frequencies of HBsAg-specific B cells remained stable. Furthermore, ALT elevation and enhanced HBsAg-specific T-cell responses following αPD-1 therapy correlated with HBsAg decline (p<0.05).Conclusions In virally suppressed CHB patients on NA therapy, 24-week half-dose sintilimab treatment demonstrated a favourable safety profile. This regimen can facilitate HBsAg reduction and even HBsAg loss, while concurrently enhancing HBV-specific T-cell responses. These findings support αPD-1 as a potential therapeutic alternative for CHB.Trial registration number NCT05769816.",
  "authors": [
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Taiyu He"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Min Chen"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Maoying Liu"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Li Zhang"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Huidan Sun"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Lu Zhang"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Aoyi Li"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Weiqun Zeng"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Ning Ling"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Xiaofeng Shi"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Hua He"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Mingli Peng"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Dachuan Cai"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Peng Hu"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Dazhi Zhang"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Yinghua Lan"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Hong Ren"
    }
  ],
  "title": "Twenty-four-week anti-PD-1 antibody regimen promoted HBsAg reduction and concurrently enhanced HBV-specific T cell responses in patients with chronic hepatitis B",
  "uid": "b1d0c7b1-9414-5705-be0e-a2a121f09df3"
}