Chronological alterations in de novo malignancies after living‐donor liver transplantation: A cohort study of 1781 recipients using annual comparisons of standardized incidence ratios

Background De novo malignancies (DNMs) are a major adverse event after solid organ transplantation; however, their characteristics and recent trends after living‐donor liver transplantation (LDLT) remain unclear. Methods We retrospectively reviewed 1781 primary LDLT recipients (1990–2020) and annually calculated standardized incidence ratios (SIRs) of DNMs compared to the age‐adjusted Japanese general population. Results After 21 845 person‐years follow‐up, 153 DNM lesions (8.6%) were identified in 131 patients (7.4%). The incidence was 0.007 person‐years. DNMs included 81 post‐transplant lymphoproliferative disorders (PTLDs), 14 colorectal, 12 lung, and 12 gastric cancers, and so on. Comorbid DNMs significantly worsened recipient survival than those without ( p < .001). The 5‐ and 10‐year recipient survival after DNM diagnosis were 65% and 58%, respectively. Notably, SIR 1993–1995 : 8.12 (95% CI: 3.71–15.4, p < .001) and SIR 1996–1998 : 3.11 (1.34–6.12, p = .01) were significantly high, but had decreased time‐dependently to SIR 2005–2007 : 1.31 (0.68–2.29, p = .42) and SIR 2008–2010 : 1.34 (0.75–2.20, p = .33), indicating no longer significant difference in DNMs development. Currently, however, SIR 2014–2016 : 2.27 (1.54–3.22, p < .001) and SIR 2017–2019 : 2.07 (1.40–2.96, p < .001) have become significantly higher again, reflecting recent aging of recipients (>50 years) and resultant increases in non‐PTLD DNMs. Furthermore, characteristically in LDLT, the fewer the donor‐recipient HLA‐mismatches, the less the post‐transplant DNMs development. Conclusion DNM development after LDLT was significantly higher than in the general population due to higher PTLD incidence (1993‐1998), but once became equivalent (2005‐2013), then significantly increased again (2014‐2019) due to recent recipient aging and resultant increase in solid cancers.