Levitsky J, et al. Biomarkers sound really cool, but are they real? The prospect of using the most promising candidate biomarkers in the practice of liver transplantation. Presented at: American Transplant Congress; June 4-8, 2022; Boston (hybrid meeting).
Schiano T, et al. Biomarkers sound really cool, but are they real? The prospect of using the most promising candidate biomarkers in the practice of liver transplantation. Presented at: American Transplant Congress; June 4-8, 2022; Boston (hybrid meeting).
Disclosures: Healio could not determine Schiano’s relevant financial information at the time of publication. Levitsky is an advisor for Mallinckrodt and also claims to be an advisor to and receive funds from Eurofins, Viracor and Transplant Genomics.
Although the development and use of biomarkers in liver transplantation has advanced in recent years, challenges and limitations remain, according to presenters at the American Transplant Congress 2022.
Thomas D. SchianoMD, professor of medicine and liver disease at Mount Sinai in New York, told participants that in transplant patients, biomarkers should monitor short- and long-term graft function, predict the development of acute and chronic diseases, assess the quality of the donor organ or monitor the response to therapeutic intervention. Additionally, biomarkers should have external validation.
“That’s the key here,” Schiano said. “They need external validation. We need more of that and the ability for repetitive assessments over time. Kidney and heart transplants are years ahead of liver transplant physicians in the development and implementation of biomarker implementation.
Advantages and limitations of biomarkers
According to Schiano, recent and ongoing studies have evaluated gene expression profiles and donor-derived cell-free DNA (dd-cfDNA), which have shown promise in guiding the management of immunosuppression, especially in the absence of hepatitis C infection.
So far, dd-cfDNA has been widely studied as a biomarker of rejection in kidney and heart transplants and in clinical practice, he said. The biomarker is not specific to any particular disease or etiology and increases with increasing liver chemistry testing, which has been a limitation.
“In the absence of hepatitis C infection, however, an increase in donor-derived cell-free DNA is more relevant for identifying allograft dysfunction,” Schiano said. “A recent and very interesting study shows that a steadily increasing proportion of donor-derived cell-free DNA precedes an elevation in liver chemistry tests in acute cellular rejection, then declines after treatment resolution of cellular rejection. acute.”
Other biomarkers studied for LT include microRNAs (miRNAs), which are organ-specific non-coding single-stranded RNA molecules.
As promising as these biomarkers are, they “all have advantages and limitations,” according to Schiano. Donor-derived cell-free DNA has a short lifespan that offers a real-time indication of liver damage, and miRNAs are liver- or immune-cell specific, making it useful to combine different miRNAs.
However, research using machine learning in post-LT is ongoing and will allow for personalized treatment strategies.
“The reality of precision medicine and day-to-day management of post-liver transplant patients is fast approaching,” Schiano said.
Biomarkers ‘must be realistic’
“Probably the best thing that happened to liver transplant was the eradication of hepatitis C,” Josh Levitsky, MD, MS, professor of medicine and surgery at Northwestern University Feinberg School of Medicine in Chicago, said during his presentation. “I think that’s a big reason why the liver has been behind the heart, kidneys and other organs — because we were focusing on hepatitis C. Now it’s not really an issue anymore. . We can really refocus on the presence of biomarkers that are not related to virus or viral reactivation and which may now be more applicable to the general population.
According to Levitsky, the field has moved towards more clinically applicable biomarkers that can be used in clinical practice, which can be taken from blood.
Current tests that examine the absence of subclinical inflammation for the minimization of immunosuppression include liver enzymes, donor-specific antibodies, and Fibroscan, while blood biomarkers such as mRNA, macroRNA, dd- cfDNA, cytokines and proteoforms are under investigation.
“We are trying to improve the monitoring of specificity rejection, but these tests are coming – hopefully very soon into clinical practice – alongside kidney and heart transplantation, where they are actually used to manage patients,” said Levitsky. “I think biomarkers are certainly cool, but they have to be realistic. The liver field has come a long way in the last 5-7 years since the eradication of hepatitis C, and I think we are getting closer to other organs.