Mount Sinai physician-scientists join DILIN to help find causes, diagnostics for drug-induced liver injury

In an effort to better understand and develop prevention strategies for drug-induced liver injury (DILI), physician-scientists from the Icahn School of Medicine at Mount Sinai have joined the Drug-Induced Liver Injury Network (DILIN), a National Institutes of Health-funded consortium of only six academic medical centers in the United States. Mount Sinai is the only center in the Northeast participating in the DILIN.

DILI affects more than one million Americans every year and is a significant cause of morbidity and mortality. Some cases require liver transplantation. Unfortunately, it is often without symptoms until the liver has been significantly damaged and the patient seeks help after developing jaundice. A number of drugs, drug interactions, and herbal supplements may cause DILI, but there are no tests to predict who is at risk for DILI and no way to diagnose this problem until it is advanced. To stimulate and facilitate research into DILI, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a division of the NIH, established the DILIN.

The Division of Liver Diseases at Mount Sinai is the latest center to join the DILIN, with Jawad Ahmad, MD, and Joseph Odin, MD, PhD, both Associate Professors of Medicine, as principal investigators. Mount Sinai's Division of Liver Diseases brings unique qualities to the consortium as the largest program of its kind in the United States, with an ethnically-diverse patient base providing a representative population of patients who suffer from DILI. Mount Sinai also has a robust Department of Genetics and Genomic Sciences, which, along with other DILIN members, may provide new opportunities to develop a genetic signature for DILI. This department is chaired by Eric Schadt, PhD, who is also the Director of the Icahn Institute for Genomics and Multiscale Biology, and the Jean C. and James W. Crystal Professor of Genomics.

"We are pleased to join the Drug-Induced Liver Injury Network to help find causes and diagnostics for drug-induced liver injury," said Dr. Ahmad. "Our inclusion in this network reflects the strength of the faculty in the Division of Liver Diseases and the Recanati/Miller Transplantation Institute, and the success of our multidisciplinary approach involving clinicians and translational scientists."

Led by Drs. Ahmad and Odin, investigators at Mount Sinai hope to shed light on the cause, risk factors and mechanisms of DILI. In conjunction with their fellow DILIN members, they will conduct retrospective analyses of drugs that are associated with a high incidence of DILI utilizing electronic medical records (EMR). Working with Dr. Schadt's group and other DILIN members, they hope to complete a Genome-Wide Association Study that will determine the genetic signature of risk for DILI, and develop a blood test based on that signature.

Drs. Ahmad and Odin will work with Erwin Bottinger, MD, Director of the Charles Bronfman Institute for Personalized Medicine, who is leading Mount Sinai's BioMe Biobank Program, an electronic medical record (EMR)-linkable repository of 27,000 consented patients with genome-wide genetic data receiving active clinical care at Mount Sinai Medical Center. Dr. Bottinger's team also created the CLIPMERGE platform, an innovative technology to integrate genetic information at the point of care in practice through EMR-enabled clinical decision support.

"Ideally, we will develop a diagnostic or predictive test that will help us better tailor treatments for our patients," said Dr. Odin. "If a patient does have the signature predicting risk, this critical information will be communicated in real-time, at the time of prescription in the office to prescribing clinicians via CLIPMERGE technology linking with EMR. This will allow clinicians to avoid certain medications for patients with predicted DILI risk. In addition, if we can find a way to prevent liver injury, we may have an opportunity to revisit medications that had previously been discarded due to liver toxicity."

Mount Sinai will receive $950,000 over five years from the NIDDK to study DILI.