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Mechanisms and Strategies for Tolerance in Liver Transplantation

  • Liver Transplantation (D Mulligan, Section Editor)
  • Published:
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Abstract

Although there has been improvement in immunosuppressive therapy in preventing acute rejection following liver transplantation, there is less progress in reducing morbidity and mortality related to immunosuppression. In particular, the use of the current maintenance agents is associated with high rates of chronic kidney disease and metabolic and neoplastic complications. The search for improved treatment algorithms includes trial and error dose minimization or even complete withdrawal; most of which have been attempted with variable success rates. These strategies would be potentially more successful if more were known about long-term immune adaptive mechanisms that occur in response to transplantation. In addition, biomarkers signifying immunoregulation or tolerance, which could more clearly define the capability of withdrawing therapy, are needed to apply a more specific approach to patient management. This review will provide an overview of the mechanisms of liver transplant tolerance and the current and future strategies for immunosuppression withdrawal.

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Abbreviations

CNI:

Calcineurin inhibitor

MMF:

Mycophenolate mofetil

mTOR:

Mammalian target of rapamycin

IS:

Immunosuppression

LT:

Liver transplant

PTLD:

Post-transplant lymphoproliferative disorder

MHC:

Major histocompatibility complex

TCR:

T-cell receptor

Treg:

Regulatory T lymphocyte

PCD:

Programmed cell death

FasL:

Fas ligand

FOXP3:

Forkhead box P3

CTLA4:

Cytotoxic T-lymphocyte-associated protein 4

IL2:

interleukin-2

IFNγ:

Interferon gamma

TGF-β:

Transforming growth factor beta

DDLT:

Deceased donor liver transplantation

LDLT:

Living donor liver transplantation

ACR:

Acute cellular rejection

CIT:

Cold ischemia time

TAC:

Tacrolimus

SRL:

Sirolimus

GcfDNA:

Graft-derived circulating cell-free DNA

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St., 19th Floor, Chicago, IL, 60611, USA

    Jennifer M. Newton & Josh Levitsky

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  1. Jennifer M. Newton
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Correspondence to Josh Levitsky.

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Jennifer Newton declares no conflict of interest.

Josh Levitsky reports personal fees from Transplant Genomics Incorporated during the course of this study.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Liver Transplantation

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Newton, J.M., Levitsky, J. Mechanisms and Strategies for Tolerance in Liver Transplantation. Curr Transpl Rep 3, 325–333 (2016). https://doi.org/10.1007/s40472-016-0119-4

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