Immunosuppression regimen and latitude impact keratinocyte carcinoma risk in U.S. liver transplant recipients.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8000462 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-069X (Electronic) Linking ISSN: 03403696 NLM ISO Abbreviation: Arch Dermatol Res Subsets: MEDLINE

Original Publication: Berlin : Springer Verlag

Liver Transplantation*/adverse effects ; Liver Transplantation*/statistics & numerical data ; Immunosuppressive Agents*/adverse effects ; Skin Neoplasms*/epidemiology ; Immunosuppression Therapy*/adverse effects; Humans ; Middle Aged ; Male ; Female ; Retrospective Studies ; Aged ; United States/epidemiology ; Risk Factors ; Incidence ; Keratinocytes/immunology ; Calcineurin Inhibitors/adverse effects ; Carcinoma, Basal Cell/epidemiology

Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54-66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02-1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34-1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02-1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08-1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management.
(© 2024. The Author(s).)

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K08 DK117013 United States DK NIDDK NIH HHS; K08-DK117013 United States DK NIDDK NIH HHS; P30-DK050306 United States DK NIDDK NIH HHS; R01-AG079911 United States AG NIA NIH HHS; R01 AG079911 United States AG NIA NIH HHS

Keywords: Immunosuppression; Keratinocyte carcinoma; Latitude; Liver transplantation

0 (Immunosuppressive Agents)
0 (Calcineurin Inhibitors)

Date Created: 20240926 Date Completed: 20240926 Latest Revision: 20241027

20241027

PMC11427564

10.1007/s00403-024-03404-3

39325226