Although increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single-center study was conducted between 1995 and 2008 and is based on 247 tacrolimus-treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 AE 2.1 vs. 7.9 AE 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR ¼ 5.42; 95% CI [1.93-15.2], p ¼ 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR ¼ 2.01; 95% CI [1.57-2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for !3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard.
There is growing evidence that liver transplantation (LT) is the most effective treatment for acute‐on‐chronic liver failure grade‐3 (ACLF‐3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF‐3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF‐3, whether or not they were listed and/or transplanted with ACLF‐3, between 2018 and 2019 were included across 20 transplantation centers. A total of 351 patients with ACLF‐3 were included: 33 had been listed prior to developing ACLF‐3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted patients with ACLF‐3 admitted to the ICU and the number listed or transplanted while in ACLF‐3 across centers. By contrast, there was a correlation between the number of patients listed and the number transplanted while in ACLF‐3. About 21% of patients who were listed while in ACLF‐3 died on the waiting list or were delisted. The percentage of LT for patients with ACLF‐3 varied from 0% to 29% for those transplanted with decompensated cirrhosis across centers (average = 8%), with an I2 index of 68% (95% confidence interval, 49%–80%), showing substantial heterogeneity among centers. The 1‐year survival for all patients with ACLF‐3 was significantly higher in centers that listed and transplanted more patients with ACLF‐3 (>10 patients) than in centers that listed and transplanted fewer: 36% versus 20%, respectively (p = 0.012). Patients with ACLF‐3 face inequity of access to LT across Europe. Waitlisting strategies for patients with ACLF‐3 influence their access to LT and, ultimately, their survival.
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