{
  "abstract": "Background Immune checkpoint inhibitors (ICIs) enable successful hepatocellular carcinoma (HCC) downstaging or bridging for liver transplantation (LT) but increase allograft rejection risk. Although immune-related adverse events (irAEs) reflect immune activation during ICI therapy, their association with post-transplant rejection remains unclear.Objective We aimed to identify the risk factors of rejection, focusing on irAEs.Design This national multicentre retrospective study included 209 adult HCC patients who received pretransplant ICIs from 2018 to 2024. Logistic regression was performed to identify rejection factors and build a predictive model. A prospective observational cohort of 23 HCC patients was enrolled to explore the association between peripheral blood immunophenotype and irAEs.Results Among 209 patients, 36 (17.2%) experienced rejection with a median time of 10 days post-LT. Multivariate analysis identified irAEs as the strongest predictor of rejection, with an OR of 9.170 (p<0.001). Other independent risk factors were recipient age <40 years (OR=3.028, p=0.049) and washout period <30 days (OR=3.071, p=0.018). The resulting predictive model achieved an area under the curve of 0.788. Moreover, patients with irAEs had significantly increased numbers of peripheral blood CD8 + T cells and higher levels of IFN-α and TNF-α versus those without (all p<0.05).Conclusions This study identified irAEs as a potent predictor of allograft rejection in HCC patients receiving pretransplant ICIs, potentially driven by heightened immune activation. The predictive model may help stratify patients at high risk of rejection.",
  "authors": [
    {
      "affiliations": [
        "Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China",
        "NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China"
      ],
      "name": "Jun Fang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China"
      ],
      "name": "Siyi Zhong"
    },
    {
      "affiliations": [
        "Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Tielong Wang"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Kang He"
    },
    {
      "affiliations": [
        "Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China",
        "NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China"
      ],
      "name": "Aibo Mu"
    },
    {
      "affiliations": [
        "Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China",
        "NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China"
      ],
      "name": "Meiching Ong"
    },
    {
      "affiliations": [
        "Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Yimou Lin"
    },
    {
      "affiliations": [
        "Department of Liver Transplantation, Organ Transplant Centre, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Zebin Zhu"
    },
    {
      "affiliations": [
        "Department of Liver Transplantation, Organ Transplant Centre, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Ning Wang"
    },
    {
      "affiliations": [
        "Department of Liver Transplantation, Organ Transplant Centre, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
        "Graduate School of Bengbu Medical College, Bengbu, Anhui, China"
      ],
      "name": "Jiancheng Wu"
    },
    {
      "affiliations": [
        "Organ Transplantation Clinical Medical Center of Xiamen University, Department of General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China"
      ],
      "name": "Zhihao Wang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing, China"
      ],
      "name": "Zhao Li"
    },
    {
      "affiliations": [
        "Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China",
        "NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China"
      ],
      "name": "Feng Gao"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China"
      ],
      "name": "Li Zhuang"
    },
    {
      "affiliations": [
        "Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China"
      ],
      "name": "Zhiyong Guo"
    },
    {
      "affiliations": [
        "Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China",
        "NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China",
        "Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China",
        "State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"
      ],
      "name": "Shusen Zheng"
    },
    {
      "affiliations": [
        "Organ Transplantation Clinical Medical Center of Xiamen University, Department of General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China"
      ],
      "name": "Hao Li"
    },
    {
      "affiliations": [
        "Department of Liver Transplantation, Organ Transplant Centre, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Shugeng Zhang"
    },
    {
      "affiliations": [
        "Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China",
        "NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China",
        "State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"
      ],
      "name": "Qi Ling"
    }
  ],
  "title": "Immune-related adverse events are a potent predictor of post-transplant rejection in HCC: a multicentre retrospective cohort study",
  "uid": "cb97d4e6-db13-5c1c-aade-30464347fb5d"
}