Sirolimus in Liver Transplant Recipients: A Large Single-Center Experience

Vivarelli, Marco; Dazzi, A.; Cucchetti, Alessandro; Gasbarrini, Antonio; Zanello, Matteo; Gioia, P. Di; Bianchi, Giampaolo; Tamé, Mariarosa; Gaudio, Massimo Del; Ravaioli, Matteo; Cescon, Matteo; Grazi, Gian Luca; Pinna, Antonio D.

doi:10.1016/j.transproceed.2010.04.045

Cited by 43 publications

(32 citation statements)

References 23 publications

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“…If confirmed in the clinic, the use of HOPE may open the door for regimens with significant low or delayed calcineurin inhibitors without a risk of graft rejection, but less toxic effects in high MELD recipients or donated after cardiac death liver transplants. 33,34 In addition, underlying recipient diseases that require minimal immunosuppressive treatment, that is, recurrent hepatitis C, 35 or advanced hepatic tumors 36 could benefit from this new strategy.…”

Section: Discussionmentioning

confidence: 99%

Hypothermic Oxygenated Perfusion (HOPE) Downregulates the Immune Response in a Rat Model of Liver Transplantation

et al. 2014

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OBJECTIVE: To evaluate the impact of a novel oxygenated perfusion approach on rejection after orthotopic liver transplantation (OLT). BACKGROUND: Hypothermic oxygenated perfusion (HOPE) was designed to prevent graft failure after OLT. One of the mechanisms is downregulation of Kupffer cells (in situ macrophages). We, therefore, designed experiments to test the effects of HOPE on the immune response in an allogeneic rodent model of nonarterialized OLT. METHODS: Livers from Lewis rats were transplanted into Brown Norway rats to induce liver rejection in untreated recipients within 4 weeks. Next, Brown Norway recipients were treated with tacrolimus (1 mg/kg), whereas in a third group, liver grafts from Lewis rats underwent HOPE or deoxygenated machine perfusion for 1 hour before implantation, but recipients received no immunosuppression. In a last step, low-dose tacrolimus treatment (0.3 mg/kg) was assessed with and without HOPE. RESULTS: Allogeneic OLT without immunosuppression led to death within 3 weeks after nonarterialized OLT due to severe acute rejection. Full-dose tacrolimus prevented rejection, whereas low-dose tacrolimus led to graft fibrosis within 4 weeks. HOPE treatment without immunosuppression also protected from lethal rejection. The combination of low-dose tacrolimus and 1-hour HOPE resulted in 100% survival within 4 weeks without any signs of rejection. CONCLUSIONS: We demonstrate that allograft treatment by HOPE not only protects against preservation injury but also impressively downregulates the immune system, blunting the alloimmune response. Therefore, HOPE may offer many beneficial effects, not only to rescue marginal grafts but also by preventing rejection and the need for immunosuppression.

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Section: Discussionmentioning

confidence: 99%

Hypothermic Oxygenated Perfusion (HOPE) Downregulates the Immune Response in a Rat Model of Liver Transplantation

et al. 2014

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“…Statement 11: Use of mTORi is recommended for patients with de novo malignancies after LT. 40,41,45-47 …”

Section: Resultsmentioning

confidence: 99%

Use of Everolimus in Liver Transplantation

et al. 2017

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Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project, named Everolimus: the road to long-term functioning, was initiated to collect the experience on EVR after LT with the aim of providing guidance for transplant clinicians. Herein, recommendations by this national consensus group, based on Delphi methodology, are presented. Consensus was reached on 20 of the 23 statements proposed, and their level of evidence, grade of recommendation, and percent of agreement are reported. Statements are grouped into 4 areas: (A) renal function; (B) time of EVR introduction, CNI reduction and elimination, and risk for graft rejection; (C) antiproliferative effects of EVR; and (D) management of EVR-related adverse events. The high level of consensus shows that there is good agreement on the routine use of EVR in predefined clinical scenarios, especially in light of posttransplant nephrotoxicity and other adverse events associated with long-term administration of CNIs.

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“…Introduction of mTOR-inhibitors to the immunosuppressive therapy protocols guided to lower tumour incidence among transplant patients in general [16]. Coadministration of sorafenib and an mTOR in- hibitor could be eff ective in patients with posttransplant HCC recurrence not suitable for radical therapy, but the toxicity and effi cacy need to be further evaluated [17].…”

Section: Discussionmentioning

confidence: 99%

The Role of Liver Transplantation in the Treatment of Hepatocellular Carcinoma – a Single Center Experience from Budapest

Piros

Görög

Fehérvári

et al. 2013

Acta Medica Marisiensis

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Background: Liver transplantation for hepatic tumours is known as a proven treatment opportunity. The outcome has improved over the past decades because of the appropriate recipient selection. Materials and methods:In a single-institution study of 29 consecutive adult patients underwent orthotopic liver transplantation (OLT) between 1 January 2004 and 1 January 2011 in the Semmelweis University, Budapest with the indication of hepatocellular carcinoma (HCC). Results: The 1-year survival was 85.7% and the 3-year survival was 71.7%. Conclusions: Further investigations are needed on the fi eld of histological and biological attributes of the hepatocellular carcinoma. Our aim is to fi nd a better and individualized immunosuppressive protocol, which is also protective against malignant tumours.

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Sirolimus in Liver Transplant Recipients: A Large Single-Center Experience

Cited by 43 publications

References 23 publications

Hypothermic Oxygenated Perfusion (HOPE) Downregulates the Immune Response in a Rat Model of Liver Transplantation

Hypothermic Oxygenated Perfusion (HOPE) Downregulates the Immune Response in a Rat Model of Liver Transplantation

Use of Everolimus in Liver Transplantation

The Role of Liver Transplantation in the Treatment of Hepatocellular Carcinoma – a Single Center Experience from Budapest

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