The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have proposed the continuation of the Drug-Induced Liver Injury Network (DILIN). As described in the RFA, DILIN will be a network composed of up to 5 Clinical Centers (CCs) with expertise in diagnosis and management of DILI and a Data Coordinating Center (DCC) with expertise in the management of multicenter studies and clinical and translational datasets. The purpose of this research program is to enhance the enrollment of cases and controls (when justified) from a diverse demographic and wide geographic distribution. The major aim of the network study is to pursue pharmacogenetic analyses to find predictive biomarkers as well as genetic "fingerprints" useful for elucidating the pathogenesis of Drug-Induced Liver Injury (DILI) and ultimately for developing specific means of prevention and or treatment. The Duke Clinical Research Institute (DCRI) proposes to continue as the DCC for DILIN. In this role, we will apply our extensive experience and research infrastructure to coordinate, support and facilitate the activities of the DILIN network. In particular, we will atted to the following specific aims: (1) Explore and Determine the use of LiverTox case report for enrollment from a wide demographic and geographic distribution throughout US;(2) Support protocol development of pharmacogenetic and biomarker studies and studies with intervention strategies to prevent and treat DILI;(3) Support development of a validated, computer-based instrument and diagnosis of DILI which is accurate, simple and practical for clinicians;(4) Support manuscript preparation;(5) Provide overall network Coordination and Logistics;(6) Ensure quality assurance and continue data management activities;(7) Contribute to maintain LiverTox;(8) Provide statistical leadership in design and analysis Issues;(9) Support ancillary studies.

Public Health Relevance

Liver injury due to medication or herbal and dietary supplement use is an important medical, scientific, and public health problem in the US. Drug-induced liver injury (DILI) is the most common reason for non-approval, withdrawal, and clinical monitoring by the FDA. Understanding the dynamics of this medical problem and determining its clinical and genetic determinants will ultimately allow safer medications to be prescribed to patient populations and safer supplement on the market.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK065176-11S1
Application #
8729098
Study Section
Special Emphasis Panel (ZDK1-GRB-N (M7))
Program Officer
Serrano, Jose
Project Start
2003-09-30
Project End
2018-06-30
Budget Start
2013-09-11
Budget End
2014-06-30
Support Year
11
Fiscal Year
2013
Total Cost
$337,253
Indirect Cost
$14,250
Name
Duke University
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Kleiner, David E; Chalasani, Naga P; Lee, William M et al. (2014) Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology 59:661-70
Fontana, Robert J; Hayashi, Paul H; Gu, Jiezhun et al. (2014) Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology 147:96-108.e4
Russo, Mark W; Hoofnagle, Jay H; Gu, Jiezhun et al. (2014) Spectrum of statin hepatotoxicity: experience of the drug-induced liver injury network. Hepatology 60:679-86
deLemos, Andrew S; Foureau, David M; Jacobs, Carl et al. (2014) Drug-induced liver injury with autoimmune features. Semin Liver Dis 34:194-204
Ghabril, Marwan; Fontana, Robert; Rockey, Don et al. (2013) Drug-induced liver injury caused by intravenously administered medications: the Drug-induced Liver Injury Network experience. J Clin Gastroenterol 47:553-8
Ghabril, Marwan; Bonkovsky, Herbert L; Kum, Clarissa et al. (2013) Liver injury from tumor necrosis factor-* antagonists: analysis of thirty-four cases. Clin Gastroenterol Hepatol 11:558-564.e3
Larion, Sebastian; Caballes, Frederick R; Hwang, Sun-Il et al. (2013) Circadian rhythms in acute intermittent porphyria--a pilot study. Eur J Clin Invest 43:727-39
Grant, Lafaine M; Kleiner, David E; Conjeevaram, Hari S et al. (2013) Clinical and histological features of idiosyncratic acute liver injury caused by temozolomide. Dig Dis Sci 58:1415-21
Ryan Caballes, F; Sendi, Hossein; Bonkovsky, Herbert L (2012) Hepatitis C, porphyria cutanea tarda and liver iron: an update. Liver Int 32:880-93
Bell, L N; Vuppalanchi, R; Watkins, P B et al. (2012) Serum proteomic profiling in patients with drug-induced liver injury. Aliment Pharmacol Ther 35:600-12

Showing the most recent 10 out of 21 publications