Biomarkers to Monitor Graft Function Following Liver Transplantation

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 bio-marker profiles from donors with unfavorable clinical characteristics