The Drug Induced Liver Injury Network (DILIN), funded by the National Institutes of Health, 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 has given important insights into DILI in the U.S. Some of the salient findings that have shaped our understanding of DILI and impact future research plans include the observation that antibiotics are the most common class of agents implicated in DILI, followed by Herbal and Dietary Supplements (HDS).
The specific aims of this o Application are as follows: 1) To accrue early DILI cases, and collect serum, tissue, and clinical information on those patients meeting entry criteria through three mechanisms: Gastroenterologist- based;electronic health record (EHR);and population-based surveillance;2) To continue to administer the DILIN Repository for Herbal and Dietary Supplements (HDS) and facilitate collaborative descriptive and product analysis and genetics research to identify injurious agents and host factors responsible for HDS induced liver injury (HILI);3) To lead DILIN's effort in the causality assessment process for HILI, including it validation, and contribute to its incorporation into a computer-based instrument that is practical for clinicians and applicable for assessment of injury due to both drugs and HDS;4) To contribute to the expansion of the Herbal and Dietary Supplement component of LiverTox and facilitate the use of LiverTox as a mechanism for DILI reporting by the medical community at large. To accomplish these aims, key collaborations have been built. Informatics specialists will assist in the design, implementation, validation, and refinement of an electronic health record algorithm. Collaborations have also been built with geneticists and the FDA toxicology group to explore the mechanisms for idiosyncratic liver injury from HDS, as well as to identify the agents responsible for injury. Our research will further refine causality assessment, particularly as it pertains to HILI. Finally, the proposed work will expand the functionality of LiverTox, both as a resource for the clinician and clinical scientist, as well as the individual seeking to report a cae of DILI or HILI.

Public Health Relevance

Liver injury can be caused by drugs and herbal-dietary supplements;injury can sometimes be severe. Our research will detect cases of liver injury early using the electronic health record and through a search for cases in partnership with the Gastroenterologists of the state of Delaware. This research will also allow us to understand how commonly this injury occurs. Finally, our research will help to identify harmful herbal-dietary supplements, and ingredients of supplements, and the mechanism by which they cause injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01DK083027-07
Application #
8627315
Study Section
Special Emphasis Panel (ZDK1-GRB-N (M7))
Program Officer
Serrano, Jose
Project Start
2008-09-30
Project End
2018-06-30
Budget Start
2013-09-03
Budget End
2014-06-30
Support Year
7
Fiscal Year
2013
Total Cost
$343,766
Indirect Cost
$113,822
Name
Albert Einstein Medical Center (Philadelphia)
Department
Type
DUNS #
148406911
City
Philadelphia
State
PA
Country
United States
Zip Code
19141
Bonkovsky, Herbert L; Barnhart, Huiman X; Foureau, David M et al. (2018) Cytokine profiles in acute liver injury-Results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group. PLoS One 13:e0206389
Dakhoul, Lara; Ghabril, Marwan; Gu, Jiezhun et al. (2018) Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers. Clin Gastroenterol Hepatol 16:722-729.e2
Ahmad, Jawad; Rossi, Simona; Rodgers, Shuchi K et al. (2018) Sclerosing Cholangitis-Like Changes on Magnetic Resonance Cholangiography in Patients With Drug Induced Liver Injury. Clin Gastroenterol Hepatol :
Church, Rachel J; Kullak-Ublick, Gerd A; Aubrecht, Jiri et al. (2018) Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort. Hepatology :
Whritenour, Jessica; Ko, Mira; Zong, Qing et al. (2017) Development of a modified lymphocyte transformation test for diagnosing drug-induced liver injury associated with an adaptive immune response. J Immunotoxicol 14:31-38
Björnsson, Einar S; Gu, Jiezhun; Kleiner, David E et al. (2017) Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes. J Clin Gastroenterol 51:63-69
Chalasani, Naga; Reddy, K Rajender K; Fontana, Robert J et al. (2017) Idiosyncratic Drug Induced Liver Injury in African-Americans Is Associated With Greater Morbidity and Mortality Compared to Caucasians. Am J Gastroenterol 112:1382-1388
Bonkovsky, Herbert L; Kleiner, David E; Gu, Jiezhun et al. (2017) Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology 65:1267-1277
Nicoletti, Paola; Aithal, Guruprasad P; Bjornsson, Einar S et al. (2017) Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study. Gastroenterology 152:1078-1089
Hayashi, Paul H; Rockey, Don C; Fontana, Robert J et al. (2017) Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology 66:1275-1285

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