Research News
Five Centers Examining Drug-Liver Damage Link
NIDDK Program Searches for Mechanisms Behind Adverse Events
Drug-induced liver injury has been a clinical issue for years, as doctors, regulators, and researchers struggle to determine what therapeutics might damage the organ. Now, an ambitious network funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is beginning to tease out information about how drugs damage the liver.
Established 2 years ago, the Drug Induced Liver Injury Network (DILIN) seeks to understand the mechanism of liver toxicity and to identify strategies to prevent adverse events in patients taking prescription drugs.
The Five DILIN Centers
University of Connecticut at Hartford Indiana University at Indianapolis University of California at San Francisco University of Michigan at Ann Arbor University of North Carolina at Chapel Hill
Two Studies Underway
The five-center network has begun two research studies. One retrospective study looks at patients who have at any time since 1994 suffered an injury after taking at least one of four different drugs known to have deleterious effects on the liver. The other seeks to recruit patients who have recently suffered a potentially severe liver injury due to drugs.
“The most important goals that the DILIN will accomplish are to establish and validate new causality instruments and collect specimens and a comprehensive database about cases that are due to drug-induced liver injury,” said José Serrano, M.D., Ph.D., who directs the network at the NIDDK. “It will become a tremendous resource that will allow the testing of hypotheses on the mechanism of injury.”
The network receives $2.25 million a year to conduct the research.
Reactions to Four Drugs Examined
The retrospective study examining past liver injuries targets reactions to four drugs: the tuberculosis treatment isoniazid; phenyton and valproic acid, which are seizure medications; and the popular antibiotic combination of amoxicillin and clavulanate, sold as Augmentin.
The two protocols have already enrolled more than 200 patients, an effort Serrano called “quite successful.” In addition to getting details about the clinical course of liver disease in those patients, researchers collect blood and other biological samples, allowing future detailed biologic and genetic analysis of the patients. The data is publicly available through the NIDDK.
Little Known about How Damage Occurs
Despite the high-profile adverse events, Serrano said researchers still know little about how such damage occurs, in part because reactions are rare and difficult to diagnose, making it harder to analyze trends. One goal of the network is building a knowledge base for understanding which patients are at risk, not simply what drugs are implicated.
“Overall, we believe that the DILIN will bring greater focus and interest to the study of drug-induced liver injury and help develop better ways to prevent, detect, and treat this growing liver problem,” said Paul Watkins, M.D., chair of the DILIN steering committee and the principal investigator at the University of North Carolina at Chapel Hill, one of the DILIN centers.
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NIH Publication No. 06–4552
May 2006
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