Blood test can spot early liver transplant issues to prevent organ failure

Liver transplant is a lifesaving surgery, but a significant number of patients experience organ rejection or other complications. Now a study by scientists from Georgetown University and MedStar Health describes how a single blood sample can be used to catch problems at the earliest stages, allowing tailored treatment to prevent the organ’s failure.

The research is a major step toward the development of a liquid biopsy that could not only quickly detect post-transplant complications but also pinpoint the cause. The technology would largely eliminate the need for more invasive tests.

The findings are published in the journal Nature Communications in a paper titled “Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant.”

“There’s a need for a much better and more granular understanding of what’s driving transplant failure,” said Anton Wellstein, MD, Ph.D., 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.”

Liver transplants are only given to patients who are in desperate need; unlike other organs like the kidneys, which can be supported with dialysis, there are no machines or treatments that can save a patient when the liver fails. And because there is just a limited supply of livers available for transplant, preventing organ injury is of paramount importance, said study co-author, Alexander Kroemer, MD, Ph.D., a transplant surgeon at MedStar Georgetown University Hospital and director of the Center for Translational Transplant Medicine at Georgetown University Medical Center.

There are several ways a transplanted organ can sustain damage. The transplantation process itself can injure the new liver, place stress on nearby organs and trigger an immune response.

Currently, transplant doctors can use blood tests to detect potential damage and genetic testing to determine whether the damaged cells originate from the donated liver or the patient’s own body. However, identifying the precise cause often requires costly imaging studies or invasive follow-up tests, such as a liver biopsy.

The new technology works by picking up DNA fragments found in the debris left behind by dying cells circulating in the bloodstream. Wellstein’s team found that chemical signatures left behind on these DNA fragments could be used to identify the original cell type and where it came from, with precise detail.

“What’s new is that we can now figure out the cellular origin of the damage,” Wellstein explained. “We can pinpoint the cell types, either in the transplanted organ or in the host, in other tissues that are getting damaged or under threat of damage.”

The convenience of the test means it can be repeated at frequent intervals, he noted, making it easier for doctors to monitor patients and detect problems early.

“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,” Kroemer said.

In addition to being faster and less invasive than a traditional tissue biopsy, the blood test is also potentially more accurate, he added.

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

When researchers started the project seven years ago, they had no idea if it would even be possible to detect cell damage in blood samples.

“It was amazing how well it worked,” Wellstein said.

The research originally started as a research project by first author Megan McNamara, an MD/Ph.D. student at Georgetown.

Georgetown has filed patent applications on the technology with Wellstein, Kroemer and McNamara named as co-inventors. The researchers are studying additional applications, including in other organ transplants, in patients receiving radiation therapy for breast cancer, and in melanoma treatment.

The team is also seeking partners to commercialize the technology for clinical settings.

“We can make the discovery—that’s where academia comes in—but if you want to translate it for use in transplantation, it has to go to industry,” he said.

Liver transplant is a lifesaving surgery, but a significant number of patients experience organ rejection or other complications. Now a study by scientists from Georgetown University and MedStar Health describes how a single blood sample can be used to catch problems at the earliest stages, allowing tailored treatment to prevent the organ’s failure.

The research is a major step toward the development of a liquid biopsy that could not only quickly detect post-transplant complications but also pinpoint the cause. The technology would largely eliminate the need for more invasive tests.

The findings are published in the journal Nature Communications in a paper titled “Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant.”

“There’s a need for a much better and more granular understanding of what’s driving transplant failure,” said Anton Wellstein, MD, Ph.D., 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.”

Liver transplants are only given to patients who are in desperate need; unlike other organs like the kidneys, which can be supported with dialysis, there are no machines or treatments that can save a patient when the liver fails. And because there is just a limited supply of livers available for transplant, preventing organ injury is of paramount importance, said study co-author, Alexander Kroemer, MD, Ph.D., a transplant surgeon at MedStar Georgetown University Hospital and director of the Center for Translational Transplant Medicine at Georgetown University Medical Center.

There are several ways a transplanted organ can sustain damage. The transplantation process itself can injure the new liver, place stress on nearby organs and trigger an immune response.

Currently, transplant doctors can use blood tests to detect potential damage and genetic testing to determine whether the damaged cells originate from the donated liver or the patient’s own body. However, identifying the precise cause often requires costly imaging studies or invasive follow-up tests, such as a liver biopsy.

The new technology works by picking up DNA fragments found in the debris left behind by dying cells circulating in the bloodstream. Wellstein’s team found that chemical signatures left behind on these DNA fragments could be used to identify the original cell type and where it came from, with precise detail.

“What’s new is that we can now figure out the cellular origin of the damage,” Wellstein explained. “We can pinpoint the cell types, either in the transplanted organ or in the host, in other tissues that are getting damaged or under threat of damage.”

The convenience of the test means it can be repeated at frequent intervals, he noted, making it easier for doctors to monitor patients and detect problems early.

“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,” Kroemer said.

In addition to being faster and less invasive than a traditional tissue biopsy, the blood test is also potentially more accurate, he added.

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

When researchers started the project seven years ago, they had no idea if it would even be possible to detect cell damage in blood samples.

“It was amazing how well it worked,” Wellstein said.

The research originally started as a research project by first author Megan McNamara, an MD/Ph.D. student at Georgetown.

Georgetown has filed patent applications on the technology with Wellstein, Kroemer and McNamara named as co-inventors. The researchers are studying additional applications, including in other organ transplants, in patients receiving radiation therapy for breast cancer, and in melanoma treatment.

The team is also seeking partners to commercialize the technology for clinical settings.

“We can make the discovery—that’s where academia comes in—but if you want to translate it for use in transplantation, it has to go to industry,” he said.