Cholongitas E, Antoniadis N, Goulis I, Theocharidou E, Ιmvrios G, Giouleme O, Filis D, Mouloudi E, Akriviadis E, Fouzas I
4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Greece; First Department of Internal Medicine, Medical School of National & Kapodistrian University, Athens, Greece.
Division of Organ Transplantation, Department of Surgery, Aristotle University Medical School, Hippokration Hospital Transplant Center, Thessaloniki, Greece.
Transplant Proc. 2019 Mar;51(2):450-453. doi: 10.1016/j.transproceed.2019.01.069. Epub 2019 Jan 29.
Everolimus, a mammalian target of rapamycin inhibitor, may have a protective role on hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but data regarding the impact of its trough serum levels on HCC recurrence are missing.
Fifty-five patients (43 men, age 55 ± 8 years) who underwent LT for HCC were evaluated. Several demographic and clinical variables were recorded, including radiological and histological characteristics of HCC as well as dosages and trough levels of immunosuppressive regimens.
HCC recurrence occurred in 11 (20%) patients: 5 (25%) of 20 patients under calcineurin inhibitors and 6 (17%) of the 35 patients under everolimus (P = .48). The patients with HCC recurrence (n = 11, group 1), compared to those without recurrence (n = 44, group 2), had significantly more frequent HCC in the explant: outside Milan criteria (P = .001), microvascular invasion (P < .001), and higher number of nodules (P = .001). In multivariate analysis, microvascular invasion was the only independent factor significantly associated with HCC recurrence (OR: 2.3, 95% CI: 1.4-10.5, P = .03). Among the patients who received everolimus-based immunosuppression, the recipients with HCC recurrence, compared to those without HCC recurrence, had significantly lower mean trough levels of everolimus at 7-12 months post-LT (3.9 vs 5.9 ng/mL, P = .001), while the patients with mean trough levels of everolimus >6 ng/mL had decreased HCC recurrence rates (log rank: 2.3, P = .007).
We found for the first time mean concentrations of everolimus between 7-12 months post-LT as the only modifiable variable related with HCC recurrence in LT recipients. However, larger studies are needed for final conclusions.
依维莫司是一种雷帕霉素哺乳动物靶点抑制剂，可能对肝移植（LT）后肝细胞癌（HCC）复发具有保护作用，但关于其血清谷浓度对HCC复发影响的数据尚缺。
对55例因HCC接受LT的患者（43例男性，年龄55±8岁）进行评估。记录了若干人口统计学和临床变量，包括HCC的影像学和组织学特征以及免疫抑制方案的剂量和谷浓度。
11例（20%）患者发生HCC复发：接受钙调神经磷酸酶抑制剂的20例患者中有5例（25%），接受依维莫司的35例患者中有6例（17%）（P = 0.48）。与未复发患者（n = 44，第2组）相比，发生HCC复发的患者（n = 11，第1组）移植肝中HCC更常见：超出米兰标准（P = 0.001）、微血管侵犯（P < 0.001）以及结节数量更多（P = 0.001）。多因素分析显示，微血管侵犯是与HCC复发显著相关的唯一独立因素（OR：2.3，95%CI：1.4 - 10.5，P = 0.03）。在接受以依维莫司为基础的免疫抑制的患者中，与未发生HCC复发的患者相比，发生HCC复发的患者在LT后7 - 12个月时依维莫司的平均谷浓度显著更低（3.9 vs 5.9 ng/mL，P = 0.001），而依维莫司平均谷浓度>6 ng/mL的患者HCC复发率降低（对数秩检验：2.3，P = 0.007）。
我们首次发现LT后7 - 12个月依维莫司的平均浓度是与LT受者HCC复发相关的唯一可改变变量。然而，需要更大规模的研究才能得出最终结论。
