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Biomarkers to Monitor Graft Function Following Liver Transplantation

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Biomarkers in Liver Disease

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Abstract

Liver transplantation (LT) has become the only curative treatment for end-stage liver disease. Patient survival has improved drastically over the years, but poor initial graft quality and complications following transplantation still limit patient and graft survival. Monitoring and evaluation of graft quality during follow-up is achieved by routine biomarker measurements in recipients’ blood, starting directly following surgery and in the months and years thereafter. This allows clinicians to early detect complications following LT, like early allograft dysfunction and biliary complications. They are also used as a tool for deciding on further diagnostics or interventions. Classic biomarkers are able to assess liver injury (aspartate and alanine aminotransferase, lactate dehydrogenase), biliary injury and obstruction (gamma-glutamyl transferase, alkaline phosphatase), and liver function (albumin, bilirubin, prothrombin time). Novel genetic markers such as microRNAs also show potential as more accurate or specific biomarker for various types of injury and functions. Some of these serum biomarkers were shown to be promising in predicting disease or severity of injury when measured in bile, though widespread implementation in clinical practice is not implemented yet. Therefore, liver biopsy remains the gold standard for diagnosing acute cellular rejection, even with less invasive serum biomarkers that are currently available. Future applications of biomarkers should enable early assessment of marginal graft function when applied to preservation solution in both simple cold storage and during ex situ machine perfusion. In the future, these developments could help to increase the donor pool for LT by optimizing and allocating grafts based on favorable biomarker profiles from donors with unfavorable clinical characteristics.

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Abbreviations

ACR:

Acute cellular rejection

AFP:

Alpha fetoprotein

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AS:

Anastomotic biliary stricture

AST:

Aspartate aminotransferase

CA 19-9:

Cancer antigen 19-9

CCA:

Cholangiocarcinoma

CDmiR:

Cholangiocyte-derived miRNA

DCD:

Donation after circulatory death

EAD:

Early allograft dysfunction

ERCP:

Endoscopic retrograde cholangiopancreatography

GGT:

Gamma-glutamyl transferase

HCC:

Hepatocellular carcinoma

HDmiR:

Hepatocyte-derived miRNA

LT:

Liver transplantation

MiRNA:

microRNA

MP:

Machine perfusion.

MRCP:

Magnetic resonance cholangiopancreatography

mRNA:

Messenger RNA

NAS:

Non-anastomotic biliary stricture

PNF:

Primary nonfunction

PSC:

Primary sclerosing cholangitis

SNP:

Single nucleotide polymorphism

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Authors and Affiliations

  1. Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Room Na-1006, P.O. Box 2040, 3000, CA, Rotterdam, The Netherlands

    Cornelia J. Verhoeven, Luc J. W. van der Laan & Jeroen de Jonge

  2. Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Room Ha-204, 2040, 3000, CA, Rotterdam, The Netherlands

    Herold J. Metselaar

  3. Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Room H-822k, P.O. Box 2040, 3000, CA, Rotterdam, The Netherlands

    Jeroen de Jonge

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  1. Cornelia J. Verhoeven
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  2. Luc J. W. van der Laan
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  3. Jeroen de Jonge
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  4. Herold J. Metselaar
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Correspondence to Herold J. Metselaar .

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  1. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

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Verhoeven, C.J., van der Laan, L.J.W., de Jonge, J., Metselaar, H.J. (2016). Biomarkers to Monitor Graft Function Following 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_20-1

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