Drug-induced liver injury (DILI) is the most common cause for acute liver failure in the U.S. DILI is also the most common safety issue leading to regulatory actions including withdrawal of drugs from the market, restrictions in indications, and warnings to physicians and patients. Fortunately, drugs that can cause liver injury are usually completely safe for the majority of patients taking them; severe DILI causing illness is an infrequent event, with an annual incidence ranging from 1 in 10,000 to 1 in 1,000,000 prescription-years. Why some people are susceptible to DILI from a particular drug is unknown. It would obviously be desirable for physicians to be able to identify these susceptible patients so that they can avoid potentially toxic medicines. Better yet would be the development of new medications that never pose a threat to the liver. These goals cannot be achieved until the mechanisms that cause DILI, and the inherited (genetic) and environmental factors that can influence these mechanisms, are defined.

Progress in this area has been hindered by the lack of clear definitions of DILI and means to confidently distinguish DILI from other types of liver disease. Also important has been the absence of a mechanism to collect data on patients with DILI, and the absence of a systematic means to collect blood and other tissues from these patients for scientific analysis.

To address these critical needs the National Institute of Diabetes, Digestive and Kidney Diseases of the United States National Institutes of Health (NIH) has recently sponsored a cooperative agreement (UO1) to create a Drug Induced Liver Injury Network (DILIN). DILIN consists of University of Michigan (PI. Robert Fontana), University of Indiana (PI. Naga Chalasani), University of Connecticut (PI. Herbert Bonkovsky), University of California, San Francisco (PI. Timothy Davern) and University of North Carolina (PI. Paul Watkins). The data coordinating center is Duke University (PI. Jim Rochon). This network began this summer to create a registry and to obtain tissues and genomic DNA from patients who have sustained severe liver injury (since 1994) due to isoniazid, phenytoin, valproic acid, and combination amoxacillin/clavulonate. In addition, the network will soon commence a second study that will prospectively enroll patients who have sustained DILI due to any medication. The data and tissues obtained in the DILIN will be made available to the scientific community, but access will be closely monitored to preserve patient confidentiality and to assure that the proposed studies are of the highest scientific quality.

"It is in everyone's interest to develop safer medicines", said Dr. Paul B. Watkins, Chairman of the DILIN Steering Committee and Professor of Medicine at the University of North Carolina. "By creating this critical resource and sharing it with scientists around the world, DILIN is a major step towards this end".

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