Graft-derived cell-free DNA as a rejection biomarker and a monitoring tool for immunosuppression in liver transplantation

Abstract

Graft-derived cell-free DNA (gd-cfDNA) can be referred to as short fragments of DNA originating from the necrosis or apoptosis of allograft cells, released into the blood. Circulating free DNA, or cell-free DNA, is a pioneering biomarker with various potentials in medical diagnosis, including the early detection of prenatal birth defects in pregnancy, cancer, and its recurrence, and allograft dysfunction in various types of transplantation. Gd-cfDNA has a short half-life (<1.5 h), and this helps detect graft injury promptly. The quantity of gd-cfDNA depends on the size of the grafted organ as well as its integrity. The principles for differentiating the donor-derived cfDNA from the recipient-derived one include a selection of single-nucleotide polymorphism, then targeted amplification and sequencing of the cfDNA in the sample. Then, the heterozygous genome in the recipient's sample is analyzed statistically and the level of dd-cfDNA is estimated. In liver transplantation, it can be applied to detect common complications such as acute rejection, personalize the immunosuppression doses according to the patient's condition, and diagnose infections associated with the transplantation. In this narrative review, we spotlight the relevance of gd-cfDNA in liver transplant, the methods used to quantify it, different types of rejections, the exclusion criteria for gd-cfDNA, and its future perspectives.

Keywords

• allograft
• biopsy
• cell-free dna
• immunosuppression
• rejection
• transplantation