De Novo Sirolimus-Based Immunosuppression After Liver Transplantation for Hepatocellular Carcinoma: Long-Term Outcomes and Side Effects

Toso, Christian; Meeberg, Glenda; Bigam, David L.; Oberholzer, José; Shapiro, AM James; Gutfreund, Klaus S.; Ma, Mang; Mason, Andrew L.; Wong, Winnie; Bain, Vincent G.; Kneteman, Norman M.

doi:10.1097/01.tp.0000262607.95372.e0

Cited by 172 publications

(150 citation statements)

References 31 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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“…Zimmerman et al [57] examined the role of sirolimusbased maintenance therapy in posttransplant recipients with a history of HCC and found that overall survival was increased in the sirolimus arm compared to the CNI arm. Clinical trials examining the anti-cancer effects of mTOR inhibitors in liver transplant recipients with HCC have been encouraging [44,58] and new trials are ongoing.…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

Overview of immunosuppression in liver transplantation

Pillai¹,

Levitsky²

2009

WJG

105

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Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease. Beginning with the revolutionary discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate periand post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon.

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“…Sirolimus-treated rats develop fewer recurrences of extrahepatic metastasis and experience enhanced survival as compared to controls [122]. A few case reports [123,124] and single-center studies [125][126][127] have demonstrated improved recurrence-free survival with the use of sirolimus from the time of transplantation. However, in the absence of level 1 studies, these results cannot be considered devoid of bias in selection or reporting.…”

Section: Immunosuppression Strategies In Patients With Hcc: Which Is mentioning

confidence: 99%

Liver Transplantation for HCC: A Review

Kakodkar¹,

Soin²

2011

Indian J Surg

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Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease or cirrhosis. Liver transplantation for hepatocellular carcinoma has the potential to eliminate both the tumor as well as the underlying cirrhosis and is the ideal treatment for HCC in cirrhotic liver as well as massive HCC in noncirrhotic liver. Limitations in organ availability, necessitate stringent selection of patients who would likely to derive most benefit. Selection criteria have considered tumor size, number, volume as well as biological features. The Milan criteria set the benchmark for tumors that would benefit from liver transplantation but were found to be excessively restrictive. Modest expansion in criteria has also been shown to be associated with equivalent survival. Microvascular invasion is the single most important adverse prognostic factor for survival. Living donor liver transplantation has expanded donor options and has the advantage of lower waiting period and not impacting the non-HCC waiting list. Acceptable outcomes have been obtained with living donor liver transplantation for larger and more numerous tumors in the absence of microvascular invasion. Downstaging of tumors to prevent progression while waiting for an organ or for reduction in size to allow enrolment for transplantation has met with variable success.

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De Novo Sirolimus-Based Immunosuppression After Liver Transplantation for Hepatocellular Carcinoma: Long-Term Outcomes and Side Effects

Cited by 172 publications

References 31 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

Overview of immunosuppression in liver transplantation

Liver Transplantation for HCC: A Review

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