Blood Test May Help Detect Liver Transplant Issues Early

A new study from Georgetown University and MedStar Health describes how circulating fragments of DNA in the bloodstream could provide a fast and accurate method to detect early signs of injury in transplanted livers.

The findings, published in Nature Communications, highlight a potential approach for identifying specific types of organ damage without the need for invasive biopsy procedures.

Detecting problems early in transplant recipients

Unlike damaged kidneys, which can be supported with dialysis, there is no similar machine or treatment that can support a patient experiencing liver failure. Liver transplants are often the only option for patients with end-stage liver disease. Yet transplantation is not without its risks. The transplantation surgery itself could injure the new liver, or the body might trigger an immune response and "reject" the organ, damaging the new liver in the process.

Traditionally, identifying liver transplant problems relies on the use of routine blood tests to detect damage and genetic testing to determine whether the damaged cells originate from the donated liver or from the response of the recipient's own body. Pinpointing the underlying cause may also necessitate the use of costly imaging studies or invasive follow-up tests, such as taking a liver biopsy.

Now, researchers have developed a method that uses circulating cell-free DNA (cfDNA) to track the source of cellular injury. By analysing the chemical signatures on these DNA fragments – specifically, patterns of DNA methylation – the researchers are able to determine the origin of damaged cells.

“There’s a need for a much better and more granular understanding of what’s driving a transplant failure,” said Anton Wellstein, MD, PhD, professor of oncology and pharmacology at Georgetown’s Lombardi Comprehensive Cancer Center and senior author of the study. “With this technology, we can draw a blood sample and pretty much get a readout of what’s going on with the whole patient.”

Tracing DNA fragments to specific cell types

The study demonstrates that the chemical modifications on cfDNA fragments can be matched to distinct cell types, offering insights into whether the injury is occurring in the donor liver or in the recipient’s own tissues. This added layer of detail could enable clinicians to deliver more targeted treatment based on the nature and location of the injury.

“If you were to know, for instance, that the biliary compartment [of the liver] is injured but not the hepatocellular compartment, you could provide a more personalized treatment approach that leads to better care for the patient,” said study co-author Alexander Kroemer, MD, PhD, a transplant surgeon at MedStar Georgetown University Hospital and director of the Center for Translational Transplant Medicine at Georgetown University Medical Center.

Identifying the precise cell type involved may also help clinicians differentiate between immune-mediated rejection and other forms of injury.

Advancing post-transplant monitoring

The new approach offers several practical advantages. Blood tests may provide a more representative picture of the organ as a whole, as they avoid the potential for sampling bias that is associated with small tissue samples.

“With needle biopsies, there’s always the potential for sampling bias, because you’re not sampling the whole liver,” Kroemer explained. “It’s just one small core that’s being evaluated.”

Another benefit of this method is its repeatability. Because blood tests can be safely performed at frequent intervals, this allows for the continuous monitoring of transplant recipients over time. This could help physicians catch early signs of transplant damage, increasing the likelihood of effective interventions taking place before irreversible damage occurs.

Although the study focused on liver transplants, the underlying technology could potentially be applied to other clinical settings. The researchers are currently exploring whether cfDNA methylation analysis could also be used to monitor injury in other types of organ transplants or even in cancer treatment settings, including in patients receiving radiation therapy for breast cancer and immunotherapy for melanoma.

Reference: McNamara ME, Jain SS, Oza K, et al. Circulating cell-free DNA methylation patterns indicate cellular sources of allograft injury after liver transplant. Nat Commun. 2025. doi: 10.1038/s41467-025-60507-9

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