Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant. 

 -  2024 
<br/><br/> Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments released from dying cells into the circulation. We analyzed 130 blood samples collected from 44 patients at different time points after transplant. Sequence-based methylation of cfDNA fragments were mapped to patterns established to identify cell types in different organs. For liver cell types DNA methylation patterns and multi-omic data integration show distinct enrichment in open chromatin and regulatory regions functionally important for the respective cell types. We find that multi-tissue cellular damages post-transplant recover in patients without allograft injury during the first post-operative week. However, sustained elevation of hepatocyte and biliary epithelial cfDNA beyond the first week indicates early-onset allograft injury. Further, cfDNA composition differentiates amongst causes of allograft injury indicating the potential for non-invasive monitoring and timely intervention. 
<br/><br/><br/>English 
<br/><br/><label>Standard No.: </label>PMC11014558 [pmc] 
<br/><br/><label>Subjects--Topical Terms: </label>--Automated
<br/><br/><label>Index Terms--Occupation: </label><br/>MedStar General Surgery Residency<br/>MedStar Georgetown University Hospital/MedStar Washington Hospital Center
<br/><br/><label>Index Terms--Function: </label><br/>Preprint