Nucleic acid biomarkers to assess graft injury after liver transplantation

Abstract

Many risk factors and complications impact the success of liver transplantation, such as ischaemia-reperfusion injury, acute rejection, and primary graft dysfunction. Molecular biomarkers have the potential to accurately diagnose, predict, and monitor injury progression or organ failure. There is a critical opportunity for reliable and non-invasive biomarkers to reduce the organ shortage by enabling i) the assessment of donor organ quality, ii) the monitoring of short- and long-term graft function, and iii) the prediction of acute and chronic disease development. To date, no established molecular biomarkers have been used to guide clinical decision-making in transplantation. In this review, we outline the recent advances in cell-free nucleic acid biomarkers for monitoring graft injury in liver transplant recipients. Prior work in this area can be divided into two categories: biomarker discovery and validation studies. Circulating nucleic acids (CNAs) can be found in the extracellular environment pertaining to different biological fluids such as bile, blood, urine, and perfusate. CNAs that are packaged into extracellular vesicles may facilitate intercellular and interorgan communication. Thus, decoding their biological function, cellular origins and molecular composition is imperative for diagnosing causes of graft injury, guiding immunosuppression and improving overall patient survival. Herein, we discuss the most promising molecular biomarkers, their state of development, and the critical aspects of study design in biomarker research for early detection of post-transplant liver injury. Future advances in biomarker studies are expected to personalise post-transplant therapy, leading to improved patient care and outcomes.

Keywords: ACR, acute cellular rejection; CIT, cold ischaemia time; CNA(s), circulating nucleic acid; EV(s), extracellular vesicles; HCC, hepatocellular carcinoma; HLA, human leukocyte antigen; LFTs, liver function tests; LT, liver transplantation; RT-qPCR, reverse-transcription quantitative PCR; TCMR, T cell-mediated rejection; biomarkers; dd-cfDNA, donor-derived cell-free DNA; ddPCR, digital droplet PCR; donor-derived DNA; extracellular vesicles; liver transplantation; miRNA, microRNA; microRNAs; molecular diagnostics; personalized therapy; transcriptomics.