HCC recurrence in HCV‐infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs – a post‐hoc analysis

HCC recurrence in HCV‐infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs – a post‐hoc analysis
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HCVâ 感染患者肝移植后 HCC 复发:SiLVER 研究揭示西罗莫司联合 CNI 的益处——事后分析

DOI:
10.1111/tri.13621
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发表时间:
2020
影响因子:
3.1
通讯作者:
Geissler EK
Geissler EK
中科院分区:
医学3区
文献类型:
--
作者:
Werner JM;Hornung M;Krah R;Götz M;Schnitzbauer AA;Schlitt HJ;Geissler EK

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影响肝细胞癌(HCC)和丙型肝炎病毒(HCV)感染的肝移植(LTx)受者结局的因素包括免疫抑制剂的选择。在这里,我们分析了HCV+亚组的患者随机对照,国际银研究。我们对166例HCV+银研究患者进行了LTx后HCC结局的随访分析。对照组患者(A组:n= 88)接受不含mTOR抑制剂(mTORi)、基于钙调磷酸酶抑制剂(CNI)的免疫抑制治疗,而西罗莫司组(B组:n= 78)接受基于西罗莫司的免疫抑制治疗。我们发现A组和B组之间的HCV-RNA滴度无显著差异。由于B组中没有效果可能是由于西罗莫司剂量可变,我们将B组分为接受西罗莫司免疫抑制+CNI的患者>50%(B1;n= 44)或<50%(B2;n= 34)的时间。虽然两组之间的HCV-RNA滴度没有差异,但B1组的HCC无复发生存率(81.8%)明显优于A组(62.7%;P= 0.0136)和B2组(64.7%;P= 0.0326);有趣的是,进一步的亚组分析显示B2组的肝酶值增加(P= 0.0012)。总之,在患有HCC和LTx的HCV感染患者中,mTORi免疫抑制+CNI产生了极好的结局。出乎意料的是,在HCV+亚组中,mTORi单药治疗发生更高水平的肝脏炎症和更差的结局。
Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV+subgroup of patients from the randomized controlled, international SiLVER Study. We performed apost hocanalysis of 166 HCV+SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A:n= 88) received mTOR inhibitor (mTORi)‐free, calcineurin inhibitor (CNI)‐based versus sirolimus‐based immunosuppression (group B:n= 78). We found no significant difference regarding HCV‐RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus‐based immunosuppression + CNIs for >50% (B1;n= 44) or <50% (B2;n= 34) of the time. While there remained no difference in HCV‐RNA titer between groups, HCC recurrence‐free survival in group B1 (81.8%) was markedly better versus both group A (62.7%;P= 0.0136) and group B2 (64.7%;P= 0.0326); Interestingly, further subgroup analysis revealed an increase (P= 0.0012) in liver enzyme values in group B2. Taken together, in HCV‐infected patients with HCC and LTx, mTORi immunosuppression + CNIs yields excellent outcomes. Unexpectedly, higher levels of liver inflammation and poorer outcomes occur with mTORi monotherapy in the HCV+subgroup.
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