Beyond biopsy and drug levels: Are TTV and dd-CFDNA the next frontiers in transplant monitoring?

Emerging biomarkers are reshaping the landscape of post-transplant surveillance by offering non-invasive, biologically meaningful insights beyond traditional biopsy and drug-level monitoring. Torque Teno Virus (TTV), a ubiquitous, non-pathogenic DNA virus, has gained attention as a surrogate marker of the host's net state of immunosuppression. Higher TTV loads correlate with increased immunosuppressive effect and heightened infection risk, while lower levels may reflect under-immunosuppression and potential rejection. Donor-derived cell-free DNA (dd-cfDNA) represents a complementary biomarker of graft integrity, released into the circulation during cellular injury, rejection, or immune-mediated damage. Combined, TTV and dd-cfDNA provide a dual-axis framework that captures both host immune tone and graft injury, offering a more nuanced, personalised approach to post-transplant management. Here, we review the biological basis, current evidence, and clinical applicability of these tools, outlines their limitations, and discusses their potential role in advancing precision immunosuppression in solid-organ transplantation.