Graft-Derived Cell-Free DNA as a Biomarker in Liver Transplantation

  • Living reference work entry
  • First Online:
Biomarkers in Liver Disease

Abstract

Improvement of long-term patient and graft outcome is still a challenge in liver transplantation. Personalized approaches to immunosuppressive treatment of liver transplant patients are currently under investigation, as conventional markers have limited usefulness to predict drug efficacy. The presence of graft-derived cell-free DNA (GcfDNA) in the plasma of liver transplant recipients opens up the possibility of monitoring allograft injury through measurement of this molecular marker. A rapid, cost-effective droplet digital PCR (ddPCR) method has been developed for the quantification of donor DNA. GcfDNA has shown to be useful for the detection of subclinical and full-blown acute rejection and non-rejection-related liver injury (e.g., HCV infection, liver trauma, ischemia/reperfusion damage). GcfDNA allows for the early detection of transplant injury (“liquid biopsy”) and enables earlier more effective treatment intervention. It is especially helpful to guide changes in immunosuppression and to monitor immunosuppression minimization. This new approach may contribute to achieve more effective, less toxic personalized immunosuppression.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AST:

Aspartate aminotransferase

cfDNA:

Cell-free DNA

ddPCR:

Droplet digital PCR

DNA:

Deoxyribonucleic acid

GcfDNA:

Graft-derived cell-free DNA

HCV:

Hepatitis C virus

HELLP:

Hemolysis, elevated liver enzymes, low platelets

ISD:

Immunosuppressive drug

LFTs:

Liver function tests

LTx:

Liver transplantation

PCR:

Polymerase chain reaction

TDM:

Therapeutic drug monitoring

WBC:

White blood cells

γ-GT:

γ-glutamyltransferase

References

  • Beck J, Bierau S, Balzer S, et al. Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury. Clin Chem. 2013;59:1732–41.

    Article  CAS  PubMed  Google Scholar 

  • Beck J, Schmitz J, Kanzow P, et al. Absolute quantification of graft derived cell-free DNA (GcfDNA) early after liver transplantation (LTx) using droplet digital PCR. Clin Chem. 2014;60(Suppl):S194–5.

    Google Scholar 

  • Beck J, Oellerich M, Schulz U, et al. Donor derived cell-free DNA is a novel universal biomarker for allograft rejection in solid organ transplantation. Transplant Proc. 2015; 47:2400–3.

    Google Scholar 

  • Crettol S, Venetz JP, Fontana M, et al. Influence of ABCB1 genetic polymorphisms on cylcosporine intracellular concentration in transplant recipients. Pharmacogenet Genomics. 2008;18:307–15.

    Article  CAS  PubMed  Google Scholar 

  • Falck P, Åsberg A, Guldseth H, et al. Declining intracellular T-lymphocyte concentration of cyclosporine a precedes acute rejection in kidney transplant recipients. Transplantation. 2008;85:179–84.

    Article  CAS  PubMed  Google Scholar 

  • Gallo A, Esquivel CO. Current options for management of biliary atresia. Pediatr Transplant. 2013;17:95–8.

    Article  PubMed  Google Scholar 

  • Gielis EM, Ledeganck KJ, De Winter BY, et al. Cell-free DNA: an upcoming biomarker in transplantation. Am J Transplant. 2015;15:2541–51.

    Google Scholar 

  • Kanzow P, Kollmar O, Schütz E, et al. Graft-derived cell-free DNA as an early organ integrity biomarker after transplantation of a marginal HELLP syndrome donor liver. Transplantation. 2014;98:e43–5.

    Article  PubMed  Google Scholar 

  • Lo YMD, Tein MSC, Pang CCP, et al. Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. Lancet. 1998;351:1329–30.

    Article  CAS  PubMed  Google Scholar 

  • Londoño MC, Danger R, Giral M, et al. A need for biomarkers of operational tolerance in liver and kidney transplantation. Am J Transplant. 2012;12:1370–7.

    Article  PubMed  Google Scholar 

  • Oellerich M, Kanzow P, Beck J, et al. Graft-derived cell-free DNA (GcfDNA) as a sensitive measure of individual graft integrity after liver transplantation. Am J Transplant. 2014a;14(Suppl3):874.

    Google Scholar 

  • Oellerich M, Schütz E, Kanzow P, et al. Use of graft-derived cell-free DNA as an organ integrity biomarker to reexamine effective tacrolimus trough concentrations after liver transplantation. Ther Drug Monit. 2014b;36:136–40.

    Article  CAS  PubMed  Google Scholar 

  • Oellerich M, Walson PD, Beck J, et al. Graft-derived cell-free DNA as a marker of transplant graft injury. Ther Drug Monit. 2016; 38(Suppl 1):575–9.

    Google Scholar 

  • Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2010; annual data report. Rockville: Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; 2011.

    Google Scholar 

  • Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2013: annual data report. Am J Transplant. 2015;15(Issue S2):4–13.

    Google Scholar 

  • Pascual M, Theruvath T, Kawai T, et al. Strategies to improve long-term outcomes after renal transplantation. N Engl J Med. 2002;346:580–90.

    Article  PubMed  Google Scholar 

  • Rodríguez-Perálvarez M, Germani G, Darius T, et al. Tacrolimus trough levels, rejection and renal impairment in liver transplantation: a systematic review and meta-analysis. Am J Transplant. 2012;12:2797–814.

    Article  PubMed  Google Scholar 

  • Rodríguez-Perálvarez M, Germani G, Papastergiou V, et al. Early tacrolimus exposure after liver transplantation: relationship with moderate/severe acute rejection and long-term outcome. J Hepatol. 2013;58:262–70.

    Article  PubMed  Google Scholar 

  • Sigdel TK, Vitalone MJ, Tran TQ, et al. A rapid noninvasive assay for the detection of renal transplant injury. Transplantation. 2013;96:97–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snyder TM, Khush KK, Valantine HA, et al. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011;108:6229–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Raemdonck D, Neyrinck A, Rega F, et al. Machine perfusion in organ transplantation: a tool for ex-vivo graft conditioning with mesenchymal stem cells? Curr Opin Org Transplant. 2013;18:24–33.

    Article  Google Scholar 

  • Yazigi NA. Long term outcomes after pediatric liver transplantation. Pediatr Gastroenterol Hepatol Nutr. 2013;16:207–18.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Oellerich .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Oellerich, M. et al. (2015). Graft-Derived Cell-Free DNA as a Biomarker in Liver Transplantation. In: Preedy, V. (eds) Biomarkers in Liver Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7742-2_10-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-7742-2_10-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-7742-2

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Navigation