S2584 De Novo Gastrointestinal Malignancies Among Liver Transplant Recipients

Introduction: De novo malignancies (DNM) are one of the most common long-term complications following liver transplantation (LT), particularly in the gastrointestinal (GI) tract. The incidence has been reported to be 2–3 times higher than in the general population. Our study sought to identify the cumulative incidence and risk factors related to GI DNM among LT recipients. Methods: We conducted a cohort study using the United Network Organ Sharing (UNOS) database, evaluating all adult LT recipients (aged 18 years or older) from 1997–2023. GI DNM included esophageal, stomach, small bowel, pancreatic, and colorectal cancers (CRC) occurring at least 1 year after LT. A competing risk regression model was used to assess cumulative incidence of GI DNM in relation to primary indication of LT and history of hepatocellular carcinoma (HCC) and/or cholangiocarcinoma (CCA) with death as a competing event. Multivariable Cox proportional hazards regression models were used to identify factors associated with GI DNM. Results: A total of 137,742 patients were analyzed; median age was 55 (IQR 48–62) years, 72.1% were White, and 20.7% had history of HCC/CCA. GI DNM occurred in 1,426 (1.0%) LT recipients (572 [40.1%] CRC, 462 [32.3%] pancreatic, 226 [15.8%] esophageal, 124 [8.6%] gastric, and 55 [3.8%] small bowel cancers). Median follow-up time was 6.4 (IQR 3.1–11.1) years. The 5-, 10-, 15-year cumulative incidence of GI DNM were highest among PSC patients (2.0, 2.8, 5.4% for PSC with HCC/CCA and 1.0, 2.3, 4.4% for PSC without HCC/CCA), followed by alcohol-associated liver disease (ALD) (1.0, 2.9, 4.5% for ALD with HCC and 0.5, 1.4, 2.3% for ALD without HCC), MASLD (1.1, 2.6, 3.6% for MASLD with HCC and 0.5, 1.2, 2.0% for MASLD without HCC), and HCV (0.6, 1.5, 2.3% for HCV with HCC and 0.3, 1.0, 1.7% for HCV without HCC). In multivariate Cox regression analysis, GI DNM developed more among older patients (aHR 1.04; CI 1.03–1.04), those with ALD (aHR 1.27; CI 1.06–1.52), PSC (aHR 2.39; CI 1.91–2.99), prior HCC (aHR 1.35; CI 1.15–1.57), and less among Hispanic patients (aHR 0.76; CI 0.63–0.93). Conclusion: In this large retrospective study, the incidence of GI DNM varied by the liver disease etiology, and the highest rates noted in patients with PSC. Age, ALD, and a history of HCC/CCA were associated with increased risk. These findings support the need of more tailored and vigilant cancer screening strategies in LT recipients.