Conversion to everolimus in maintenance liver transplant patients: A multicenter, retrospective analysis

Saliba, Faouzi; Dharancy, Sébastien; Lorho, R.; Conti, Filoména; Radenne, Sylvie; Néau-Cransac, Martine; Hurtova, Monika; Hardwigsen, Jean; Calmus, Yvon; Dumortier, Jérôme

doi:10.1002/lt.22292

Cited by 75 publications

(79 citation statements)

References 48 publications

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“…A multicenter retrospective analysis in 240 LTx patients demonstrated similar adverse effects with EVRL [28]. Mean white blood count decreased significantly and total cholesterol and triglyceride levels increased significantly.…”

Section: Pharmacology Of M-torimentioning

confidence: 86%

“…Preconversion albuminuria (>30 mg/L) and high SRL trough levels (>9.5 lg/L) were significant risk factors for SRL treatment withdrawal. Recently, a multicenter study of 240 patients converted to EVRL a mean of 4.9 years after liver transplant was e-published[51]. In the complete cohort, estimated GFR improved from 64.2 ml/min at day 0 to 68.4 ml/min at month 12 after LTx; no control group (CNIs alone) was included in this study.…”

mentioning

confidence: 99%

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m-TOR inhibitors: What role in liver transplantation?

Kawahara

Asthana

Kneteman

2011

Journal of Hepatology

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The development of calcineurin inhibitors (CNIs) led to marked improvements in patient and graft survival after liver transplantation (LTx). We have been left, however, with a dependence on immunosuppressive agents with nephrotoxicity, neurotoxicity, adverse impacts on cardiac risk profile, and risk for malignancy. These challenges need to be met against a dominance of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) as indications for liver transplant. Unmet needs for immunosuppression (IS) in LTx include: (1) Effective drugs that avoid CNIs toxicities. (2) Agents without adverse impact on HCV recurrence. (3) Compounds that minimize risk of HCC recurrence. New immunosuppressives will need to address the above needs while supporting patient and graft survival equivalent to those achievable with CNIs, ideally without important new toxicities. Two new classes of agents are currently in advanced clinical development: belatacept, and the mammalian target of rapamycin inhibitors (m-TORi). This manuscript will review evidence for a role for m-TORi in LTx in a range of clinical scenarios including patients with CNI nephrotoxicity or neurotoxicity, patients at risk of (or with) HCV recurrence, and patients at risk of HCC recurrence.

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Section: Pharmacology Of M-torimentioning

confidence: 86%

mentioning

confidence: 99%

m-TOR inhibitors: What role in liver transplantation?

Kawahara

Asthana

Kneteman

2011

Journal of Hepatology

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“…In Jeng et al [22] 's singlecentre prospective non-randomised study, HCC recurred in 7% of the patients using EVR. In retrospective studies, it has been observed that EVR has no HCC recurrence post-LT during a mean follow-up of 11.2 ± 6.8 mo in 44 patients and 48 mo (range: 11-76 mo) in 21 patients respectively [26,36] . In a systematic review, LT recipients who were on mTOR inhibitors (sirolimus or EVR) had lower HCC recurrence rates [37] .…”

Section: Prevention Of Hepatocellular Carcinoma Recurrencementioning

confidence: 99%

Use of Everolimus in Liver Transplantation

2017

Transplantation

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In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation (LT) setting. The efficacy of everolimus (EVR) in de novo LT is established and a reasonable time to initiate EVR is 30 d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor (CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy. Adverse effects of proteinuria, hypercholesterolemia and hyperlipidemia are significantly higher as compared to standard CNI and long-term implications on graft and patient survival in LT is still unclear. Future research to explore strategies to minimise EVR adverse effects will be crucial for the success of EVR as an important alternative or adjunct immunosuppressive therapy in LT. Core tip: Everolimus is the most recently approved immunosuppressant for use in liver transplantation (LT). Its renoprotective effect is an attractive option for LT recipients who have calcineurin inhibitor-induced nephrotoxicity. This review examines through data published, discovers gaps of evidences and discusses the place in therapy for everolimus (EVR) in LT. At the end of review, it summarises how EVR can benefit LT recipients as well as the caveat in using EVR.Yee ML, Tan HH. Use of everolimus in liver transplantation.

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“…Regarding everolimus, there are some data to suggest that it can protect against HCC recurrence after transplant as well as to be of use in the management of patients with recurrent HCC after transplant (70,71). Data from phase 1 and 2 studies showed a stabilization of HCC progression with everolimus (72,73).…”

Section: Mammalian Target Of Rapamycin Inhibitors (Mtor)mentioning

confidence: 99%