Novel electronic health record-based marker can identify at-risk transplant patients and reduce organ rejection
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A new multicenter study led by researchers at the Icahn School of Medicine at Mount Sinai suggests that a novel electronic health record-based marker can help clinicians identify transplant patients at high risk for organ rejection because they are not taking their medications as prescribed—and intervene before the rejection happens.
The study, published in the American Journal of Transplantation, evaluated the use of the medication level variability index (MLVI), a new objective marker derived from routine lab values, to flag adolescents and young adults at elevated risk following liver transplantation.
Conducted across 13 pediatric transplant centers in the United States and Canada, the randomized controlled trial screened more than 3,000 health records of patients who had undergone liver transplantation. A total of 148 participants identified as high risk based on MLVI were assigned either to standard care or to a two-year remote behavioral intervention designed to support consistent medication use.
While the study did not reach statistical significance for its primary endpoint—a combined measure of rejection, retransplantation and consent withdrawal—this was because rejection rates were lower than expected in both groups. Even so, patients in the intervention group experienced about half as many rejection-related events and retransplants as those receiving standard care. Importantly, the routine use of MLVI as a risk marker across study sites appeared to substantially reduce overall rejection rates, bringing them down to levels typically seen in low-risk patients.
"What this study shows is that we can identify patients who are not taking their medications as prescribed using data we already have in the electronic health record—and act before serious complications occur," said Eyal Shemesh, MD, chief of the Division of Behavioral and Developmental Health at Mount Sinai Kravis Children's Hospital and the principal investigator of this study. "Even without a statistically significant primary outcome, the clinical implication is clear: We can now know who is at risk, and focus our efforts and resources there, leading to substantially improved outcomes." Shemesh is also a professor of pediatrics and psychiatry at the Icahn School of Medicine at Mount Sinai.
Medication nonadherence is a leading cause of organ rejection, particularly among adolescents and young adults, yet clinicians have long lacked reliable tools to detect it early. Unlike traditional approaches that rely on self-reporting or resource-intensive monitoring, MLVI uses variability in routine immunosuppressant blood levels to identify inconsistent medication-taking behavior. Because transplant patients—even if they inconsistently take their medications—periodically undergo closely monitored blood testing to assess medication levels and graft health, researchers were able to use fluctuations in these routinely collected lab values as an objective marker of elevated risk.
The study also demonstrated that a remote, telehealth-based intervention—delivered through regular check-ins with trained specialists—can engage even high-risk patients over an extended period, including throughout the COVID-19 pandemic, as the trial both kept patients engaged and enrolled new patients during that time.
"Adherence has always been one of the most challenging issues we face in transplant medicine, because staying on track with complex medical care can be overwhelming, especially for adolescents," said Benjamin L. Shneider, MD, senior author of the study, chief of gastroenterology, hepatology and nutrition at Texas Children's, and George Peterkin Endowed Chair and professor of pediatrics at Baylor College of Medicine.
"This work shows it is possible to recognize nonadherence early and address it before it leads to life-threatening consequences. By using tools like the MLVI, we can help more pediatric liver transplant patients stay healthy, prevent rejection and spend less time in the hospital. Further, these findings may improve care not only for transplant patients, but for all patients and families managing chronic diseases."
"The findings of this team are incredibly impactful: The lessons from this trial have many positive implications for the field's next steps in optimizing our patients' lifelong health by early identification and correction of behaviors that put our patients at risk," said George Mazariegos, MD, chief of pediatric transplantation at UPMC Children's Hospital in Pittsburgh, an author of the study and the chair of the Starzl Network for Excellence in Pediatric Transplantation, a learning network that includes North America's leading pediatric transplant centers.
Researchers emphasize that while the intervention itself requires further study to determine the most efficient and cost-effective model, the findings strongly support incorporating MLVI into routine clinical practice.
"This approach allows clinicians to move from reacting to rejection to preventing it," Shemesh added. "That shift has the potential to change transplant care."
Publication details
Eyal Shemesh et al, A remote intervention to improve medication nonadherence guided by a marker of risk derived from the electronic health records of adolescent transplant recipients., American Journal of Transplantation (2026). DOI: 10.1016/j.ajt.2026.04.030
Journal information: American Journal of Transplantation
Key medical concepts
Liver TransplantationMedication Non Adherence
Clinical categories
PediatricsGastroenterologyCommon illnesses & Prevention Provided by The Mount Sinai Hospital Who's behind this story?
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