Noninvasive graft monitoring using donor‐derived cell‐free DNA in Japanese liver transplantation

Abstract

AbstractAimTo evaluate the use of donor‐derived cell‐free DNA (dd‐cfDNA) in diagnosing graft injuries in Japanese liver transplantation (LTx), including family‐related living donors.MethodsA total of 321 samples from 10 newly operated LTx recipients were collected to monitor the early dynamics of dd‐cfDNA levels after LTx. Fifty‐five samples from 55 recipients were collected during protocol biopsies (PB), whereas 36 samples from 27 recipients were collected during event biopsies, consisting of 11 biopsy‐proven acute rejection (AR), 20 acute dysfunctions without rejection (ADWR), and 5 chronic rejections. The levels of dd‐cfDNA were quantified using a next‐generation sequencer based on single nucleotide polymorphisms.ResultsThe dd‐cfDNA levels were elevated significantly after LTx, followed by a rapid decline to the baseline in patients without graft injury within 30 days post‐LTx. The dd‐cfDNA levels were significantly higher in the 11 samples obtained during AR than those obtained during PB (p < 0.0001), which decreased promptly after treatment. The receiver operator characteristic curve analysis of diagnostic ability yielded areas under the curve of 0.975 and 0.897 for AR (rejection activity index [RAI] ≥3) versus PB and versus non‐AR (ADWR + PB). The dd‐cfDNA levels during AR were elevated earlier and correlated more strongly with the RAI (r = 0.740) than aspartate aminotransferase/alanine aminotransferase. The dd‐cfDNA levels were neither associated with graft fibrosis based on histology nor the status of donor‐specific antibodies in PB samples.ConclusionsDonor‐derived cell‐free DNA serves as a sensitive biomarker for detecting graft injuries in LTx. Further large‐scale cohort studies are warranted to optimize its use in differentiating various post‐LTx etiologies.