Pre-transplant hepatocellular carcinoma is associated with increased risk of post-transplant non-HCC cancer in liver transplant recipients.

Background Post-transplant malignancy (PTM) contributes substantially to late morbidity and mortality after liver transplantation (LT), yet contemporary data on cancer spectra across cirrhosis etiologies remain limited. We assessed PTM prevalence, determinants, and cancer-type distribution by pre-LT etiology in a Canadian cohort to inform risk-adapted surveillance in routine practice.Methods We conducted a retrospective cohort study of adults undergoing LT at a tertiary Ontario center (2007–2018) with 60-month follow-up. De novo and recurrent malignancies were ascertained through June 2023 using institutional cancer registries. Time-to-event associations with post-LT cancers were evaluated using Cox proportional hazards models.Results Among 575 recipients (mean age 53.6 ± 11.0 years; 30.1% women), etiologies included alcohol-associated liver disease (22.9%), HCV (20.8%), MASLD (16.2%), PSC (11.1%), and others. Maintenance immunosuppression was predominantly tacrolimus with or without mycophenolate. Overall, 55 patients (9.5%) developed non-HCC cancers at 27.3 ± 19.1 months; the most frequent were non-melanoma skin cancer (3.4% of the cohort; 36.4% of cancers), head and neck (10.9%), PTLD (9.1%), and gastrointestinal (9.1%). Post-LT HCC occurred in 3.4% (90% recurrences). Overall cancer incidence was similar across etiologic groups, but cancer-type distributions differed (p = 0.049). In multivariable Cox models, age, sex, smoking, alcohol use, and immunosuppression class were not associated with non-HCC cancer risk, whereas pre-LT HCC independently increased risk (HR 2.66; 95% CI 1.40–5.08; p = 0.003).Conclusions PTM was common after LT and overall showed etiology-linked cancer spectra. These findings support universal dermatologic surveillance and intensified, individualized screening for recipients with pre-transplant HCC, incorporating underlying liver disease etiology to optimize early detection and long-term outcomes.