Much progress has been made in the field of hepatotoxicity since the death of Hyman J. Zimmerman, MD, a pioneer in this area of research. Over the past 20 years, several groups around the world have begun to study patients with idiosyncratic drug induced liver injury (DILI) in prospective registries to improve understanding of the risk factors, etiological agents, and natural history of DILI.
Robert J. Fontana, MD, FAASLD, Professor of Internal Medicine and Medical Director of Liver Transplantation at the University of Michigan will tap into his own experience with the condition and his work in one of these groups during this year’s Hyman J. Zimmerman Hepatotoxicity State-of-the-Art Lecture “Idiosyncratic DILI: Lessons Learned from Bedside to Bench.”
“In the past, research started with a problem in the clinics. We go to the lab to figure out the science of how and why it happens to come up with treatments and preventions,” said Dr. Fontana, who is a clinical investigator with particular expertise in DILI and acute liver failure. “With this disease, it’s pretty uncommon in the general population so we’ve not been able to do that because if the incidence is of the disease is really low, it’s hard to make progress on rare diseases.”
But due to a concerted effort on the part of physicians and researchers dedicated to raising awareness of the problem, that has changed. Since 2004, Dr. Fontana has been a principal investigator and Co-Chair of the Drug Induced Liver Injury Network (DILIN) Steering Committee, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. This group and others around the globe have been collecting and analyzing cases of severe liver injury caused by prescription drugs, over-the-counter drugs, and herbal and dietary supplements.
In addition to helping design the ongoing studies, Dr. Fontana has helped lead efforts to improve causality assessment and identify the genetic, immunological, and environmental determinants of early adverse outcomes, chronic liver injury, and other clinical outcomes in DILI patients. He has also conducted ancillary studies in EMR mining, pharmacogenetic analyses, and DILI biomarkers.
“Now that the research networks are collecting valuable biological samples along with detailed clinical data, we are now going back to the lab and trying to identify susceptibility factors,” he said. “In the lecture, I hope to review what we have learned. Do we have better diagnostic tests or methods? Do we have a better prognostic test? Do we understand the pathways in the immune system and the liver that are involved?”
Dr. Fontana noted one disturbing trend related to DILI in the United States: the growing use of herbal and dietary supplements that are unregulated by the Food and Drug Administration which may contain mixtures of potentially hepatotoxic ingredients.
“There have been outbreaks where people have taken seemingly benign supplements, and they became very ill and needed a transplant. This is a growing public health problem. So, one of the goals of my lecture is to raise everyone’s awareness regarding this issue,” he said. “There’s a lot of committed talented people working on this, but we all need to work on it together. When you have a rare disease, you need to have other doctors refer their patients to where research is being done.”
While progress has been made into understanding the risk factors, etiological agents, and natural history of DILI, Dr. Fontana hopes to emphasize more work is needed.
“We have just begun to scratch the surface, but we are a lot smarter and nimbler and we are certainly better able to phenotype or characterize patients in 2016 than we were in 1999,” he said. “We’ve raised awareness in the liver and GI communities and the general public of the potential for adverse drug events that can involve the liver. We are starting to do mechanistic studies back in the lab and having some successes with genetic associations with DILI in the HLA region. In addition, we are beginning to identify sensitive and specific biomarkers for DILI diagnosis that were not available in 1999, but we still have a long way to go.”
Hyman J. Zimmerman Hepatotoxicity State-of-the-Art Lecture
10:00 am – 10:30 am Monday
CC: Auditorium and Balcony