The Drug Induced Liver Injury Network (DILIN), funded by the National Institutes of Health in 2002, represents a critical strategy to mitigate the adverse consequences of DILI. Already, this extensive network of centers around the U.S. has cultivated an impressive repertoire of case-based clinical information and samples which will broaden our understanding of DILI. Initial work centered around retrospective data collection on DILI attributable to four drugs;amoxicillin/clavulanate, valproic acid, phenytoin, and isoniazid. Subsequent work, which is ongoing, involves the prospective accrual of incident cases of DILI from any drug or complementary and alternative medication. The purpose of this grant application is to contribute to the expansion of the DILIN through the participation of a large Philadelphia-based consortium;the Jefferson and University of Pennsylvania Health Systems represent the largest and second largest health care systems in the region, respectively. They draw adult and pediatric patients with hepatic disease from the region comprising Eastern Pennsylvania, Delaware, Southern and Central New Jersey, and Northern Maryland. Hepatology leaders from these health care systems have agreed to collaborate as a single clinical center for his grant. In addition, the Geisinger Health System will participate as a subsite of Jefferson;this component will extend the consortium's reach to include a large part of central Pennsylvania. The consortium will bring to DILIN a large ethnically and socioeconomically diverse population of patients.
The specific aims of this proposal are as follows: 1) To identify bona fide adult and pediatric cases of DILI within the region comprising Eastern and Central Pennsylvania, Maryland, Delaware, and Southern and Central New Jersey;2) To validate the accuracy of disease attribution, in conjunction with other members of DILIN;3) To support a national network of centers devoted to the advancement of pharmacogenetic and pharmacoepidemiological study of DILI, by providing clinical information and samples;and 4) To participate in the development and maintenance of a website for use as an educational resource on DILI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK083027-05
Application #
8330956
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (O1))
Program Officer
Serrano, Jose
Project Start
2008-09-30
Project End
2012-09-30
Budget Start
2012-07-01
Budget End
2012-09-30
Support Year
5
Fiscal Year
2012
Total Cost
$73,144
Indirect Cost
$15,034
Name
Thomas Jefferson University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
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
Hayashi, Paul H; Fontana, Robert J; Chalasani, Naga P et al. (2015) Under-reporting and Poor Adherence to Monitoring Guidelines for Severe Cases of Isoniazid Hepatotoxicity. Clin Gastroenterol Hepatol 13:1676-82.e1
Martinez, Melissa A; Vuppalanchi, Raj; Fontana, Robert J et al. (2015) Clinical and histologic features of azithromycin-induced liver injury. Clin Gastroenterol Hepatol 13:369-376.e3
Fontana, Robert J; Hayashi, Paul H; Barnhart, Huiman et al. (2015) Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol 110:1450-9
Alqahtani, Saleh A; Kleiner, David E; Ghabril, Marwan et al. (2015) Identification and Characterization of Cefazolin-Induced Liver Injury. Clin Gastroenterol Hepatol 13:1328-1336.e2
Foureau, D M; Walling, T L; Maddukuri, V et al. (2015) Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis. Clin Exp Immunol 180:40-51
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

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