Reduced calcineurin inhibitor exposure with antibody induction and recurrent hepatocellular carcinoma after liver transplantation

医学 他克莫司 肝移植 免疫抑制 钙调神经磷酸酶 肝细胞癌 米兰标准 内科学 胃肠病学 比例危险模型 移植 前瞻性队列研究
作者
Jenny Abrahamsson,Malin Sternby Eilard,Magnus Rizell,William M. Bennett,Fredrik Åberg
出处
期刊:Scandinavian Journal of Gastroenterology [Taylor & Francis]
卷期号:57 (3): 325-332 被引量:4
标识
DOI:10.1080/00365521.2021.2010799
摘要

Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT), but post-LT tumor recurrence remains a concern. Early post-LT immunosuppression is suggested to affect recurrence risk. We evaluated the impact on HCC recurrence of an immunosuppression protocol introduced in 2010 with interleukin-2 receptor antibody (IL-2RA) induction and delayed-introduction of reduced-dose tacrolimus with mycophenolate.We included consecutive HCC patients transplanted 2000-2017 in Gothenburg. The impact on HCC recurrence of IL-2RA induction and mean tacrolimus trough concentration during the first 20 post-LT days was analyzed by multivariable Cox regression and propensity score-adjusted analyses.The study comprised 235 patients (mean age 57 yrs, men 80%, mean MELD 13, within Milan criteria 57%). The cumulative 5-yr HCC recurrence rate among patients transplanted before and after 2010 were 28.6% and 19.7%, respectively. IL-2RA induction had no independent effect on HCC recurrence. High tacrolimus exposure (mean 20-day tacrolimus concentration ≥8ng/mL) was associated with increased HCC recurrence risk on univariable analysis (HR 2.22, 95% CI 1.23-4.01, p = .008), but was non-significant on multivariable analysis (p = .17). Outside Milan criteria, high tacrolimus exposure was significant for HCC recurrence (HR 3.68, 95% CI 1.34-10.11, p = .012) independently of tumor characteristics and AFP level. This was confirmed on multivariable propensity score-adjusted analysis.Reduced early tacrolimus exposure, facilitated by IL-2RA induction, was associated with reduced risk for HCC recurrence among patients outside Milan criteria. Prospective studies are needed to confirm if early tacrolimus-minimization strategies can help reduce HCC recurrence rates and help extend transplant criteria.
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