{
  "abstract": "This review examined the association between calcineurin inhibitor (CNI) exposure and de novo malignancy risk in liver transplant recipients. A comprehensive electronic search was conducted in PubMed, Medline and Cochrane Library until April 2025. All the articles obtained were then included in the review if they met the inclusion criteria. A total of nine studies with a population of 6829 recipients investigating the association between CNI exposure and increased malignancy risk were included in the review. Some studies revealed divergent risks between CNI types, for instance the association of cyclosporine with higher solid tumour risk compared with tacrolimus. A single study reported a potential dose-dependent relationship, suggesting high tacrolimus exposure was associated with a 1.71-fold to 2.3-fold increase in de novo malignancy risk. The narrative synthesis of the nine included studies revealed a predominant association between CNI and non-melanoma skin cancer and upper aerodigestive cancers. Among the key risk factors associated with increased de novo malignancies in patients treated with CNIs are age (>60 years), male gender, smoking history and time since transplantation correlating with malignancy incidence. Two individual studies reported that CNI minimisation strategies, including early withdrawal protocols, were associated with reductions in malignancy incidence ranging from 35% to 42% for combination therapy with malian target of rapamycin (mTOR) inhibitors. In one study, conversion to mycophenolate mofetil monotherapy was associated with an 84% reduction in malignancy risk. These findings support personalised immunosuppression approaches tailored to individual risk profiles. Nonetheless, further prospective studies are needed to optimise CNI regimens that balance rejection prevention and long-term oncological safety. PROSPERO registration number : CRD420251082749.",
  "authors": [
    {
      "affiliations": [
        "Multiorgan Transplant Centre of Excellence, Liver Transplantation Unit, King Fahad Specialist Hospital, Dammam, Eastern Province, Saudi Arabia",
        "Faculty of Medicine, Department of Medicine, Zamzam University College, Khartoum, Sudan"
      ],
      "name": "Eyad Gadour"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania",
        "Advanced Regional Research Centre of Gastroenterology and Hepatology, University of Medicine and Pharmacy Victor Babes, Timișoara, Romania"
      ],
      "name": "Bogdan Miutescu"
    },
    {
      "affiliations": [
        "Liver and Small Bowel Health Centre, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh, Riyadh Province, Saudi Arabia"
      ],
      "name": "Ehab Abufarhaneh"
    },
    {
      "affiliations": [
        "Multiorgan Transplant Centre of Excellence, Liver Transplantation Unit, King Fahad Specialist Hospital, Dammam, Saudi Arabia"
      ],
      "name": "Hadi Kuriry"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Victor Babes Timisoara, Timișoara, Romania",
        "Advanced Regional Research Centre of Gastroenterology and Hepatology, University of Medicine and Pharmacy Victor Babes Timisoara, Timișoara, Romania"
      ],
      "name": "Camelia Nica"
    },
    {
      "affiliations": [
        "Multiorgan Transplant Centre of Excellence, Liver Transplantation Unit, King Fahad Specialist Hospital, Dammam, Eastern Province, Saudi Arabia"
      ],
      "name": "Lameyaa Alsheekh"
    },
    {
      "affiliations": [
        "Liver and Pancreatobiliary Disease Research Centre, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Tehran Province, Iran (the Islamic Republic of)"
      ],
      "name": "Ehsaneh Taheri"
    },
    {
      "affiliations": [
        "Multiorgan Transplant Centre of Excellence, Liver Transplantation Unit, King Fahad Specialist Hospital, Dammam, Eastern Province, Saudi Arabia"
      ],
      "name": "Zahra A Al Saeed"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Faculty of Medicine, Pharmacy and Dental Medicine, \"Vasile Goldis” West University of Arad, Arad, Romania"
      ],
      "name": "Oana Koppandi"
    },
    {
      "affiliations": [
        "Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Riyadh Province, Saudi Arabia",
        "Department of Medicine, Alfaisal University, Riyadh, Riyadh Province, Saudi Arabia"
      ],
      "name": "Faisal Abaalkhail"
    },
    {
      "affiliations": [
        "Multiorgan Transplant Centre of Excellence, Liver Transplantation Unit, King Fahad Specialist Hospital, Dammam, Eastern Province, Saudi Arabia",
        "Department of Surgery, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia"
      ],
      "name": "Mohammed Saad Alqahtani"
    }
  ],
  "title": "Calcineurin inhibitor exposure and de novo malignancy risk in liver transplant recipients: a narrative review of dose-dependent effects, risk factors and minimisation strategies",
  "uid": "ab09e3c1-eae5-5617-82f7-a32fef21370a"
}