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Biomarkers in Liver Disease pp 99–128Cite as

Liver Transplantation Biomarkers in the Metabolomics Era

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Abstract

The term biomarker usually refers to the biochemical molecules used in basic and clinical research, and also in the clinical practice, as surrogate markers that offer the advantage of being an objective, quantifiable, and reproducible measure. The most common applications of biomarkers include diagnosis, screening and monitoring of disease, assessment of response during therapy, risk assessment, and prognosis. Metabolomics or metabonomics enables the determination of hundreds of small molecules at the same time, which provides more comprehensive information than the determination of a single biomarker. Using metabolomics as an approach for searching biomarkers is supported by its capabilities to detect subtle metabolic changes triggered by external stimuli or perturbation. Metabolome changes are quite dynamic compared to genomics and transcriptomics, or even proteomics. Therefore, such metabolite alterations are found early in different samples, like tissues, cell lysates, blood, serum, plasma, feces, urine, etc. Application of metabolomics in liver transplantation is still in its early stages and has focused mainly on studying three aspects: post-reperfusion damage and rejection and dysfunction of the organ. In the current era when lack of organs suitable for transplantation is the most important limiting factor, the existence of an accepted functional assessment of grafts before transplantation would help to not only recover initially discarded organs but to also assess the therapies used to improve the quality of these organs. Different metabolic approaches have been used to search for objective markers of graft function and quality, but further analytical and clinical validation in multicentre studies is mandatory before they are incorporated into clinical routines.

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Abbreviations

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

ADMA:

Asymmetric dimethylarginine

BA:

Bile acids

DBD:

Donation after brain dead

DCD:

Donation after circulatory dead

C18:

Aliphatic chain of length 18

CEAD:

Colorimetric electrochemical array detection

CIT:

Cold ischemia time

CS:

Cold storage

EAD:

Early allograft dysfunction

ECD:

Extended criteria donor

FT-ICR MS:

Fourier transform ion cyclotron resonance mass spectrometry

FXR:

Farnesoid X receptor

GC:

Gas chromatography

HILIC:

Hydrophilic interaction liquid chromatography

HPLC:

High-performance liquid chromatography

HR-MAS H-NMR:

High-resolution magic angle spinning

H-NMR:

Proton nuclear magnetic resonance spectroscopy

IGF:

Initial good function

IP-LC:

Ion-pairing liquid chromatography

IRI:

Ischemia reperfusion injury

JNK:

c-Jun N-terminal kinase

LC:

Liquid chromatography

LT:

Liver transplant

MRM:

Multiple reaction monitoring

NIH:

National Institute of Health

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NMP:

Normothermic machine perfusion

OPLS-DA:

Orthogonal projection to latent structures-discriminant analysis

PCA:

Principal component analysis

PLS:

Partial least square

PLS-DA:

Partial least square-discriminant analysis

PNF:

Primary non-function

QC:

Quality control

Q-ToF:

Quadrupole time of flight

ROS:

Reactive oxygen species

Rt:

Retention time

RP:

Reversed phase

TQ:

Triple quadrupole

UPLC:

Ultraperformance liquid chromatography

WHO:

World Health Organization

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Acknowledgments

This work has been supported by the European Regional Development Fund, the Carlos III Health Institute of the Spanish Ministry of Economy and Competitiveness (PI14/0026), and by the Roche Organ Transplantation Research Foundation. A. L. is grateful for a Miguel Servet II contract (CPII14/0004) from the above Ministry/Carlos III Health Institute.

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Authors and Affiliations

  1. Liver Transplant Unit, Institute of Liver Studies, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK

    Miriam Cortes

  2. Unidad de Hepatología Experimental, Unidad Analítica, Instituto de Investigación Sanitaria, Fundación Hospital La Fe, Avenida Fernando Abril Martorell 106, 46026, Valencia, Spain

    Juan Carlos García-Cañaveras, Eugenia Pareja & Agustín Lahoz

  3. Unidad de Cirugía Hepato-Bilio-Pancreatica y Trasplante Hepático, Hospital Universitario y Politécnico La Fe de Valencia, Avenida Fernando Abril Martorell 106, 46026, Valencia, Spain

    Eugenia Pareja

Authors
  1. Miriam Cortes
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  2. Juan Carlos García-Cañaveras
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  3. Eugenia Pareja
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  4. Agustín Lahoz
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Corresponding author

Correspondence to Agustín Lahoz .

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Editors and Affiliations

  1. Department of Biomedical Science, Faculty of Science and Technology, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

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Cortes, M., García-Cañaveras, J.C., Pareja, E., Lahoz, A. (2017). Liver Transplantation Biomarkers in the Metabolomics Era. In: Patel, V., Preedy, V. (eds) Biomarkers in Liver Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7675-3_42

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