Hepatotoxicity due to prescription medications and herbal supplements is increasingly recognized as a major cause of morbidity and mortality throughout the developed world. Due to its idiosyncratic nature, variable presentation, and the vast number of potential causative drugs as well as herbal and dietary supplements, drug-induced liver injury (DILI) is often diagnosed late in its course when patients present with severe liver disease. This makes diagnosis and characterization of the mechanisms involved in the pathogenesis of DILI, difficult and does not allow accurate assessment of the epidemiology and risk factors associated with DILI. Since one of the main concerns with the current DILIN is the late presentation of cases, future investigation should focus on accruing cases where the liver injury is detected early on.
The aims of the Mount Sinai membership in the NIDDK DILI study are as follows: 1) To rapidly increase the number of enrolled adults and children with DILI, particularly among under-represented minority groups in the current DILIN prospective and retrospective databases;2) To enroll patients early in the course of DILI by closely monitoring high risk groups;and 3) ultimately to investigate preventative measures to prevent DILI among high risk groups. The inclusion of Mount Sinai in the DILIN will lead to an increase in the number of DILI cases from Hispanic, Black and Asian patients. The significant number of Asian and Hispanic patients who will be recruited from the New York area may provide insights into the mechanism of liver injury related to the use of herbal and dietary supplements as these populations are known to be frequent users of these complementary and alternative medicines. A major component of the Mount Sinai DILIN will be focused on the recruitment of elderly patients with DILI, and importantly also on a control population taking these supplements, a population not well represented to date in the network. Similarly, Mount Sinai's large population of 4,000 HIV infected patients will provide cases and controls to represent the large population on antiretroviral therapy. The large number of patients undergoing chemotherapy treatment followed by the many Mount Sinai oncologists represents another ideal source of prospective DILI cases and controls. Mount Sinai is a member of eMERGE, a national consortium to develop, disseminate, and apply approaches using electronic medical records (EMR) systems to genomics research. A current projects in eMERGE is to develop an electronic algorithm to identify cases of DILI in EMR systems. If just 1 percent of the 100,000 eMERGE DNA samples have a history of DILI, then the DILIN could double its DNA sample database overnight. Investigators at Mount Sinai are well-qualified and poised to contribute to ancillary studies that arise from the wealth of available data and samples of the collective DILIN. Combined with outstanding infrastructure to collect detailed information through exploitation of the EMR and Data Warehouse, the partnership of the Personalized Medicine program, and involvement of a multi-disciplinary team across the institution and its affiliates, we bring tremendous manpower to bear upon this urgent problem.

Public Health Relevance

Due to the often idiosyncratic nature and the vast number of potential causative drugs, as well as herbal and dietary supplements, drug-induced liver injury (DILI) is typically diagnosed late in its course when patients present with severe liver disease. We will recruit patients early in the course of DILI and also follow patients who are at high risk f developing DILI to improve understanding of this insidious condition. Mount Sinai is home to a large and diverse patient base that will enhance quality and quantity of data produced by this consortium of contributing medical centers.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1-GRB-N (M7))
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Serrano, Jose
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Icahn School of Medicine at Mount Sinai
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Heidemann, Lauren A; Navarro, Victor J; Ahmad, Jawad et al. (2016) Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case Series. Dig Dis Sci 61:2741-8
Bonkovsky, Herbert L; Kleiner, David E; Gu, Jiezhun et al. (2016) Clinical Presentations and Outcomes of Bile Duct Loss caused by Drugs and Herbal and Dietary Supplements. Hepatology :
Zheng, Elizabeth X; Rossi, Simona; Fontana, Robert J et al. (2016) Risk of Liver Injury Associated with Green Tea Extract in SLIMQUICK(®) Weight Loss Products: Results from the DILIN Prospective Study. Drug Saf 39:749-54
Usachov, Valentyn; Urban, Thomas J; Fontana, Robert J et al. (2015) Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury. BMC Med 13:196
Chalasani, Naga; Bonkovsky, Herbert L; Fontana, Robert et al. (2015) Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology 148:1340-52.e7