The Einstein Medical Center will continue to recruit cases for the three DILIN protocols; prospective, retrospective, and acute, and to participate in all of its procedures and ancillary studies. At Einstein, we will focus our investigative approach on liver injury from Herbal and Dietary Supplements (HDS). Specifically, our approach will entail expansion of prospective enrollment of DILI cases due to HDS, especially those with early injury, using an innovative marketing method termed Search Engine Optimization, whereby the internet will be exploited as a recruitment tool. We will support ongoing chemical analysis of HDS collected from DILIN enrollees in collaboration with the National Center for Natural Products Research (NCNPR) at the University of Mississippi. In order to more fully characterize liver injury associated with HDS, we will oversee several activities. First, we will participate with Dr. David Kleiner from the NIH in a detailed review of the histopathology associated with liver injury from HDS by informing his review with chemical analysis and detailed clinical information. Second, we will oversee a case-by-case review of previously adjudicated cases, taking into consideration newly available chemical analyses of HDS, proposing adjustment to final causality determinations as appropriate. Third, we will, conduct a nested case/control study to identify those factors associated with use of HDS that affect the odds of developing liver injury. This grant will also explore the toxicity of HDS, focusing on Green Tea Extract, a commonly used ingredient of HDS for which there is significant evidence for toxicity; our findings will provide guidance to scientists, regulators, and consumers on the safe use of this ingredient, and define an approach to further research with other natural product ingredients. Finally, we will reduce the turn-around time for product analysis, thus refining the DILIN causality assessment process by incorporating chemical analysis results into its adjudication process. This quicker turn- around time will also facilitate pharmacovigilance efforts in collaboration with the Food and Drug Administration. We will also collaborate with the CDC to support an eventual early warning system for outbreaks of liver injury due to HDS by providing product and de-identified case information on confirmed cases of liver injury due to HDS; this information will allow the detection of outbreaks of attributable liver injury. To support all of our aims, we will continue to oversee and DILIN HDS repository as a critical resource of the DILIN.
Herbal and dietary supplements are a common cause of hepatotoxicity among patients with liver injury. Our research will deepen the understanding of the clinical presentation of cases by more fully characterizing the histology, the chemical composition of products implicated in liver injury, and the circumstances of use that may affect the likelihood of developing injury. We will also establish important conduits for information that will promote public health and product safety to the Food and Drug Administration and Centers for Disease Control and Prevention.
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