First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece.
Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.
Clin Transplant. 2023 May;37(5):e14957. doi: 10.1111/ctr.14957. Epub 2023 Mar 7.
Everolimus, a selective inhibitor of mamalian target of rapamycin (mTORi), is considered to be an alternative immunosuppressive regimen in the liver transplantation (LT) setting. However, most of the transplant centers avoid its early use (i.e., during the first month) after LT mainly due to safety issues.
We searched for all articles published between 01/2010 and 7/2022 to evaluate the effectiveness and safety of initial/early administration of everolimus after LT.
Seven studies (three randomized controlled trials and four prospective cohort studies) were included: initial/early everolimus-including therapy (group 1) was used in 512 (51%) and calcineurin inhibitor (CNI) based therapy (group 2) in 494 (49%) patients. No significant difference was found between group 1 and group 2 patients regarding the rates of biopsy-proven acute rejection episodes (Odds Ratio [OR]: 1.27, 95% CI: .67-2.41, p = .465) and hepatic artery thrombosis (OR: .43, 95% CI: .09-2.02, p = .289). Everolimus was associated with higher rates of dyslipidemia (14.2% vs. 6.8%, p = .005) and incisional hernia (29.2% vs. 10.1%, p < .001). Finally, no difference was found between the two groups regarding recurrence of hepatocellular carcinoma (Risk Rates [RR]: 1.22 95%CI: .66-2.29, p = .524) and mortality (RR: .85 95%CI: .48-1.50, p = .570).
Use of initial/early everolimus seems to be effective with a satisfactory safety profile, making its administration a reasonable therapeutic option in the LT setting.
依维莫司是一种哺乳动物雷帕霉素靶蛋白（mTOR）的选择性抑制剂，被认为是肝移植（LT）背景下的另一种免疫抑制方案。然而，大多数移植中心主要由于安全性问题而避免在 LT 后早期（即术后第一个月内）使用依维莫司。
我们检索了 2010 年 1 月至 2022 年 7 月期间发表的所有文章，以评估 LT 后依维莫司早期给药的有效性和安全性。
纳入了 7 项研究（3 项随机对照试验和 4 项前瞻性队列研究）：512 例患者接受了依维莫司初始/早期治疗（组 1），494 例患者接受了钙调磷酸酶抑制剂（CNI）为基础的治疗（组 2）。组 1 和组 2 患者之间在活检证实的急性排斥反应发生率（优势比 [OR]：1.27，95%CI：.67-2.41，p=0.465）和肝动脉血栓形成（OR：0.43，95%CI：.09-2.02，p=0.289）方面无显著差异。依维莫司与更高的血脂异常发生率（14.2%vs.6.8%，p=0.005）和切口疝发生率（29.2%vs.10.1%，p<0.001）相关。最后，两组间肝细胞癌复发（风险比 [RR]：1.22，95%CI：.66-2.29，p=0.524）和死亡率（RR：0.85，95%CI：.48-1.50，p=0.570）无差异。
依维莫司早期使用似乎是有效的，且具有令人满意的安全性，使其成为 LT 背景下的一种合理治疗选择。
