Trough Levels of Everolimus Are Associated With Recurrence Rates of Hepatocellular Carcinoma After Liver Transplantation

Antoniadis, Nikolaos; Goulis, Ioannis; Theocharidou, Eleni; Ιmvrios, G.; Γιουλεμέ, Όλγα; Filis, D.; Mouloudi, Eleni; Akriviadis, Evangelos; Fouzas, I.

doi:10.1016/j.transproceed.2019.01.069

Cited by 12 publications

(11 citation statements)

References 5 publications

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“…Regarding HCC recurrence, literature data including large cohort studies and meta‐analyses are contradictory, while the only randomized control study with sirolimus showed no impact on HCC recurrence 21 . Nevertheless, well designed studies have shown that relatively high trough levels of CNIs, particularly during the first month after LT, are associated with increased risk for HCC recurrence, 2 while higher exposure to mTORi (everolimus trough levels more than 6 ng/ml) may be related with lower rates of HCC recurrence 4 . Despite these advantages, mTORi are not preferred during the first month after LT in most transplant centers, since sirolimus has been associated with increased risk for hepatic artery thrombosis.…”

Section: Discussionmentioning

confidence: 99%

“…Mammalian target of rapamycin inhibitors (mTORi), that is, sirolimus and everolimus, represent an alternative immunosuppressive option in the LT setting, since several studies have shown that mTORi (in contrast to CNIs or mycophenolate mofetil [MMF]) may also exhibit both immunosuppressive and anti‐neoplasmatic properties 3 . Thus, early initiation of mTORi seems to have important clinical implications in the management of patients who are transplanted for HCC achieving lower levels of CNIs and relatively high mTORi levels (e.g., everolimus trough levels more than 6 ng/ml) during the first post‐operative period 4 . Regarding renal dysfunction, mTORi have established beneficial renal profile and most studies support the main message of “the sooner the better” that is, prompt initiation of mTORi before severe deterioration of glomerular filtration rate (GFR) occurred.…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of everolimus initiation from the first month after liver transplantation: A systematic review and meta‐analysis

Burra

Vourli

Papatheodoridis

2023

Clinical Transplantation

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Introduction: 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. Methods: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.Results: 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

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of everolimus initiation from the first month after liver transplantation: A systematic review and meta‐analysis

Burra

Vourli

Papatheodoridis

2023

Clinical Transplantation

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“…Cholongitas et al . recently reported that among the patients who received EVL‐based immunosuppression, the recipients with HCC recurrence, compared to those without HCC recurrence, had significantly lower mean trough levels of EVL at 7–12 months post‐LT (3.9 vs 5.9 ng/ml, P = 0.001), while the patients with mean trough levels of EVL > 6 ng/ml had decreased HCC recurrence rates (log rank: 2.3, P = 0.007) [49]. Therefore, keeping EVL blood concentration above a certain level may be important to produce anti‐tumoral effect, probably via inhibiting a downstream effector of PI3K/Akt signaling.…”

Section: Discussionmentioning

confidence: 99%

High trough levels of everolimus combined to sorafenib improve patients survival after hepatocellular carcinoma recurrence in liver transplant recipients

et al. 2021

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Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) occurs in 10%-20% of patients transplanted for HCC. The treatment of HCC recurrence after LT remains a challenge. Consecutive patients who underwent LT for HCC between 2005 and 2015 at our center were recruited. Characteristics of patients with recurrence, modalities of treatment and outcome were collected retrospectively. Patient survival was analyzed according to HCC recurrence therapeutic strategy. Among 306 transplanted patients, 43 patients (14.1%) developed recurrence with a median survival time after recurrence of 10.9 months (95%CI: 6.6À18.6). Survival of patients treated with Sorafenib (SOR) and everolimus (EVL) (n = 19) was significantly better than that of the group treated with other strategies (n = 24) (P = 0.001). Multivariable analysis demonstrated that SOR plus EVL therapy and absence of dissemination at diagnosis of recurrence were independent predictive factors of prolonged survival after recurrence. Among the patients who treated with EVL, survival of patients with controlled EVL blood trough levels ≥5 ng/ml was significantly better compared to those with EVL trough levels <5 ng/ml (P = 0.021). Combination therapy of sorafenib and everolimus was an independent predictor for better survival after HCC recurrence. Patients with controlled everolimus trough level ≥5 ng/ml might get the best survival benefit.

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“…Everolimus treatment proved not to be associated with tumor recurrence, neither at multivariate Cox regression nor in a competing-risk analysis for tumor recurrence death, in a study including 192 HCC patients undergoing liver transplantation [ 118 ]. Blood trough levels seem to be associated with HCC recurrence rate, and were found to be significantly higher in patients with recurrence [ 119 ]. On the contrary, a monocentric retrospective study demonstrated that patients treated with everolimus in combination with CNIs had significantly better time to recurrence and OS compared to those receiving CNIs alone [ 120 ].…”

Section: Management Of Hcc Recurrencementioning

confidence: 99%

Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation

Pelizzaro

Gambato

Gringeri

et al. 2021

Cancers

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Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10–15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.

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Trough Levels of Everolimus Are Associated With Recurrence Rates of Hepatocellular Carcinoma After Liver Transplantation

Cited by 12 publications

References 5 publications

Safety and efficacy of everolimus initiation from the first month after liver transplantation: A systematic review and meta‐analysis

Safety and efficacy of everolimus initiation from the first month after liver transplantation: A systematic review and meta‐analysis

High trough levels of everolimus combined to sorafenib improve patients survival after hepatocellular carcinoma recurrence in liver transplant recipients

Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation

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