Sirolimus Therapy in Liver Transplant Patients: An Initial Experience at a Single Center

Nocera, Arcangelo; Andorno, Enzo; Tagliamacco, Augusto; Morelli, N; Bottino, G; Ravazzoni, Ferruccio; Casaccia, M.; Barocci, S; Alice, S.; Santori, Gregorio; Ghirelli, R.; Valente, Umberto

doi:10.1016/j.transproceed.2008.05.005

Cited by 31 publications

(38 citation statements)

References 6 publications

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“…67 When sirolimus is used for immunosuppression after transplant in HCC patients, multiple retrospective studies and case reports have revealed trends of lower recurrence rate and metastasis of HCC after LT. [68][69][70][71][72][73][74][75][76][77][78] However, the timing of when to start mTOR inhibitors after LT is debatable, particularly with early reports of hepatic artery thrombosis when sirolimus is used immediately after transplant. 79,80 It is also unclear if mTOR should be used at the time of HCC recurrence.…”

Section: Sirolimusmentioning

confidence: 99%

“…58,59,61,[89][90][91] Alternatively, there have been several smaller prospective studies on sirolimus, which showed encouraging results in LT patients at high risk for HCC recurrence when used as the de novo immunosuppressive agent and in combination with tacrolimus, in addition to the many retrospective studies, which revealed beneficial outcomes in patients on sirolimus for immunosuppression who have recurrent HCC. [66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] While promising, there are many unanswered questions regarding the use of sorafenib and sirolimus such as the timing of their introduction after transplant and the length of treatment. Prospective randomized controlled studies evaluating the immunosuppressive regimen in HCC patient's undergoing LT, as well as treatment modalities for recurrent HCC including surgical approaches and systemic chemotherapies are eagerly anticipated in the near future.…”

Section: Sorafenibmentioning

confidence: 99%

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Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

Rubin

Ayoub²,

Kaldas³

et al. 2012

Exp Clin Transplant

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Hepatocellular carcinoma is the most common form of liver cancer, representing 70% to 85% of primary hepatic malignancies in adults. Liver transplant is an optimal treatment for patients with hepatocellular carcinoma because it eliminates the malignancy as well as the oftenunderlying liver cirrhosis and restores normal liver function. Since the development of strict selection criteria in hepatocellular carcinoma patients undergoing liver transplant with the implementation of the Milan criteria, patient survival and recurrence rates after liver transplant have dramatically improved. However, several research groups are now seeking to expand this criteria to include more patients with larger tumors who may achieve similar postliver transplant survival rates as those patients meeting current eligibility requirements. Currently, in approximately 20% of patients, hepatocellular carcinoma recurrence is still the rate-limiting event that clearly affects patient survival.Given the limited number of grafts available for transplant, the poor prognosis of untreated hepatocellular carcinoma, and the recent notion of expanding selection criteria, strategies for reducing the rate of, monitoring and treating hepatocellular carcinoma recurrence, in both pretransplants and posttransplants, are explored in this review. We review the available literature to better understand current strategies available to optimize long-term clinical outcomes.

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Section: Sirolimusmentioning

confidence: 99%

Section: Sorafenibmentioning

confidence: 99%

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

Rubin

Ayoub²,

Kaldas³

et al. 2012

Exp Clin Transplant

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“…A number of retrospective studies [10,[67][68][69][70][71] and two nonrandomized analyses of prospectively-collected data [72,73] have evaluated HCC recurrence or patient survival in liver transplant patients receiving de novo mTOR inhibitor therapy from the time of transplant (Table 3). In each of these studies, patients were also given CNI therapy.…”

Section: Retrospective Studiesmentioning

confidence: 99%

“…Menon et al undertook a systematic analysis of recurrence and survival in patients transplanted for HCC according to use or non-use of sirolimus from the time of transplant [74], based on five observational studies [10,69,70,72,73] which included a total of 474 patients. In one of the three studies, patients under sirolimus also received CNI therapy [10].…”

Section: Pooled Analysesmentioning

confidence: 99%

mTOR inhibitor therapy: Does it prevent HCC recurrence after liver transplantation?

Duvoux

Toso

2015

Transplantation Reviews

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“…The diverse actions of rapamycin on the immune response justify its candidacy as a treatment for autoimmune hepatitis, and limited experiences after liver transplantation have supported its further study in this disease [210][211][212][213][214]. The use of rapamycin has not been reported in patients with autoimmune hepatitis outside of liver transplantation, and this experience has been meager but promising.…”

Section: Rapamycinmentioning

confidence: 99%

Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I

Czaja¹

2012

IADT

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Nonstandard drugs that target critical pathogenic pathways or immune regulatory mechanisms constitute the next generation of treatments for autoimmune hepatitis. Mycophenolate mofetil impairs the proliferation of lymphocytes, decreases autoantibody production, and induces apoptosis of activated immunocytes. Patients treated for azathioprine intolerance improve more frequently than patients treated for refractory liver disease (54% versus 10%), and mycophenolate mofetil is emerging as a rescue therapy for this population. Complete corticosteroid withdrawal is possible in 40% of patients treated with mycophenolate mofetil, and the frequency of side effects ranges from 3-34%. Budesonide in combination with azathioprine has normalized liver tests more frequently (47% versus 18%) and with fewer side effects (28% versus 53%) than standard therapy after 6 months. Budesonide is emerging as a frontline treatment in non-cirrhotic patients with uncomplicated disease or contraindications to conventional corticosteroids. Cyclosporine and tacrolimus are effective salvage agents for steroid-refractory disease, but side effects have been common and occasionally serious. The 6- thioguanine nucleotides and rapamycin are feasible treatments for autoimmune hepatitis, but 6-thioguanine has major obstacles to overcome, especially the risk of liver toxicity or nodular regenerative hyperplasia. The nonstandard drug therapies emerging for autoimmune hepatitis reflect the need to supplement or supplant current treatment regimens. None has been licensed for use in autoimmune hepatitis, and their applications have been based on results from small singlecenter experiences.

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Sirolimus Therapy in Liver Transplant Patients: An Initial Experience at a Single Center

Cited by 31 publications

References 6 publications

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

mTOR inhibitor therapy: Does it prevent HCC recurrence after liver transplantation?

Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I

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