Can immunosuppression be stopped after liver transplantation?

Clavien, Pierre‐Alain; Muller, Xavier; Oliveira, Michelle; Dutkowski, Philipp; Sánchez‐Fueyo, Alberto

doi:10.1016/s2468-1253(16)30208-4

Cited by 34 publications

(40 citation statements)

References 63 publications

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“…These studies demonstrate that tolerant recipients present stable graft function after IS weaning in the longterm follow-up and that complete withdrawal of IS drugs could be safely achieved in more than one quarter of carefully selected LT recipients without compromising patients and grafts survival (9,40).…”

Section: Operational Tolerance After Liver Transplantationmentioning

confidence: 65%

“…Despite our study population is still relatively small, we believe that perhaps all LT recipients who had HCC prior to transplant should attempt IS minimization schedules and, whenever possible, complete IS withdrawal as soon as possible after LT. The selection of patients who attempt IS tapering is essential for the good outcome, in particular by the identification of non-invasive transcriptional and/or serological biomarkers of tolerance (9,40).…”

Section: Discussionmentioning

confidence: 99%

“…So far, a complete withdrawal of IS drugs after LT has been reported to be safely achievable in 25% of patients (defined as "operational tolerant"), without the risk of graft loss (8). IS weaning has the benefit of reducing IS-related side effects such as infections, diabetes, renal failure, cardiovascular diseases and de novo tumours (9)(10)(11). Therefore, in HCC-LT recipients, IS withdrawal could theoretically contribute to reduce the risk of tumour recurrence, which represents the major drawback in these recipients.…”

Section: Introductionmentioning

confidence: 99%

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Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Angelico

Parente

Manzia

2017

Transl. Gastroenterol. Hepatol.

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Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT) is still up to 15-20%, despite a careful selection of candidates and optimization of the management within the waiting list. To reduce tumour recurrence, the currently adopted post-transplant strategies are based on the administration of a tailored immunosuppression (IS) regimen. Drug-induced depression of the immune system is essential in preventing graft rejection, however has a well-established association with oncogenesis. The immune system has a key role as a defending mechanism against cancer development, preventing vascular invasion and metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the aim to minimize drugs' doses, is essential to gain the optimal balance between the risk of rejection and the risk of tumour recurrence. So far, a complete withdrawal of IS drugs after LT is reported to be safely achievable in 25% of patients (defined as "operational tolerant"), without the risk of patient and graft loss. The recent identification of non-invasive "bio-markers of tolerance", which permit to identify patients who could successfully withdraw IS therapies, opens new perspectives in the management of HCC after LT. IS withdrawal could potentially reduce the risk of tumour recurrence, which represents the major drawback in HCC recipients. Herein, we review the current literature on IS weaning in patients who underwent LT for HCC as primary indication and we report the largest experiences on IS withdrawal in HCC recipients.

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Section: Operational Tolerance After Liver Transplantationmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Angelico

Parente

Manzia

2017

Transl. Gastroenterol. Hepatol.

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“…Most LT recipients require lifelong immunosuppression, although some develop ‘operational tolerance’ and can maintain graft health without immunosuppression 11 12. Maximum immunosuppression is required early post-transplant, when rejection risk is greatest.…”

Section: How Should Immunosuppression Be Managed In the Clinic?mentioning

confidence: 99%

Adult liver transplantation: UK clinical guideline - part 2: surgery and post-operation

Millson

Considine

Cramp

et al. 2020

Frontline Gastroenterol

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Survival rates for patients following liver transplantation exceed 90% at 12 months and approach 70% at 10 years. Part 1 of this guideline has dealt with all aspects of liver transplantation up to the point of placement on the waiting list. Part 2 explains the organ allocation process, organ donation and organ type and how this influences the choice of recipient. After organ allocation, the transplant surgery and the critical early post-operative period are, of necessity, confined to the liver transplant unit. However, patients will eventually return to their referring secondary care centre with a requirement for ongoing supervision. Part 2 of this guideline concerns three key areas of post liver transplantation care for the non-transplant specialist: (1) overseeing immunosuppression, including interactions and adherence; (2) the transplanted organ and how to initiate investigation of organ dysfunction; and (3) careful oversight of other organ systems, including optimising renal function, cardiovascular health and the psychosocial impact. The crucial significance of this holistic approach becomes more obvious as time passes from the transplant, when patients should expect the responsibility for managing the increasing number of non-liver consequences to lie with primary and secondary care.

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“…It is now well recognized that the liver exhibits numerous intrinsic immunoregulatory properties that contribute to a unique propensity toward spontaneous acceptance in the context of transplantation and to a far lower risk of graft loss secondary to rejection episodes, as compared with other transplanted organs [3][4][5][6][7][8]. For example, successful LT can be done without human leukocyte antigen (HLA) matching, across a positive crossmatch, with lower immunosuppressive requirements than other organs, and liver allografts can recover from advanced acute and chronic rejection episodes [4,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of immune tolerance in liver transplantation

Vionnet

Sánchez‐Fueyo

2018

Human Immunology

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The liver exhibits intrinsic immune tolerogenic properties that contribute to a unique propensity toward spontaneous acceptance when transplanted, both in animal models and in humans. Thus, in contrast to what happens after transplantation of other solid organs, several years following liver transplantation a significant subset of patients are capable of maintaining normal allograft function with histological integrity in the absence of immunosuppressive drug treatment. Significant efforts have been put into identifying sensitive and specific biomarkers of tolerance in order to stratify liver transplant recipients according to their need for immunosuppressive medication and their likelihood of being able to completely discontinue it. These biomarkers are currently being validated in prospective clinical trials of immunosuppression withdrawal both in Europe and in the United States. These studies have the potential to transform the clinical management of liver transplant recipients by mitigating, at least in part, the burden of lifelong immunosuppression.

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Can immunosuppression be stopped after liver transplantation?

Cited by 34 publications

References 63 publications

Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

Adult liver transplantation: UK clinical guideline - part 2: surgery and post-operation

Biomarkers of immune tolerance in liver transplantation

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