title: Conversion from Calcineurin Inhibitor-Based Immunosuppression to Mycophenolate Mofetil in Monotherapy Reduces Risk of De Novo Malignancies After Liver Transplantation.
abstract: BACKGROUND Immunosuppression increases the risk of malignancy in liver transplant recipients. The potential impact of mycophenolate mofetil monotherapy on this risk has not been studied. MATERIAL AND METHODS The incidence and risk factors for de novo malignancies of 392 liver transplant recipients with a survival higher than 3 months and a mean follow-up of 8.5 years were studied. RESULTS De novo malignancies were diagnosed in 126 patients (32.1%) (64 non-melanoma skin cancer and 81 other malignancies). Sixty-nine patients (18.1%) stopped receiving calcineurin inhibitors and were maintained on mycophenolate mofetil monotherapy. The proportion of time on mycophenolate mofetil monotherapy (obtained after dividing the time on monotherapy by the time until diagnosis of neoplasia/last follow-up) was independently associated with a lower risk of de novo malignancy (HR: 0.16, 95% CI: 0.05-0.48; P=0.001), non-melanoma skin cancer (HR: 0.17, 95% CI: 0.03-0.79; P=0.024), and other malignancies (HR: 0.23, 95% CI: 0.07-0.77; P=0.017). Older age and male sex were also associated with a higher risk of malignancy, and transplantation for hepatocellular carcinoma increased the risk of non-melanoma skin cancer. CONCLUSIONS Mycophenolate mofetil monotherapy is associated with a lower risk of cancer in liver transplant recipients compared with maintenance immunosuppression with calcineurin inhibitors.
authors.affiliation: Department of Internal Medicine, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Aguiar
authors.affiliation: Department of Internal Medicine, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Martínez-Urbistondo
authors.affiliation: Liver Unit, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.|Network Center of Biomedical of Liver and Digestive Diseases Hepáticas y (CIBERehd), Pamplona, Navarra, Spain.|Institute of Health Research of Navarra (IdiSNA), Pamplona, Navarra, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: D'Avola
authors.affiliation: Liver Unit, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.|Network Center of Biomedical of Liver and Digestive Diseases Hepáticas y (CIBERehd), Pamplona, Navarra, Spain.|Institute of Health Research of Navarra (IdiSNA), Pamplona, Navarra, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Iñarrairaegui
authors.affiliation: Network Center of Biomedical of Liver and Digestive Diseases Hepáticas y (CIBERehd), Pamplona, Navarra, Spain.|Institute of Health Research of Navarra (IdiSNA), Pamplona, Navarra, Spain.|Department of Surgery, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardo
authors.affiliation: Network Center of Biomedical of Liver and Digestive Diseases Hepáticas y (CIBERehd), Pamplona, Navarra, Spain.|Institute of Health Research of Navarra (IdiSNA), Pamplona, Navarra, Spain.|Department of Surgery, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rotellar
authors.affiliation: Liver Unite, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.|Network Center of Biomedical of Liver and Digestive Diseases Hepáticas y (CIBERehd), Pamplona, Navarra, Spain.|Institute of Health Research of Navarra (IdiSNA), Pamplona, Navarra, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.affiliation: Liver Unite, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.|Network Center of Biomedical of Liver and Digestive Diseases Hepáticas y (CIBERehd), Pamplona, Navarra, Spain.|Institute of Health Research of Navarra (IdiSNA), Pamplona, Navarra, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Quiroga
authors.affiliation: Liver Unit, Clinica Universidad de Navarra, Pamplona, Navarra, Spain.|Network Center of Biomedical of Liver and Digestive Diseases Hepáticas y (CIBERehd), Pamplona, Navarra, Spain.|Institute of Health Research of Navarra (IdiSNA), Pamplona, Navarra, Spain.
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Herrero
mesh_terms: D000367:Age Factors; D000368:Aged; D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000601:surgery; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D008113:Liver Neoplasms / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology*; D012306:Risk; D012737:Sex Factors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid