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AASLD-FDA-NIH-PhRMA Hepatotoxicity Steering Group Meeting, 2006 Presentations: Method of DILIN in establishing causality

Don Rockey, MD 
Professor of Medicine and Chief, Division of Digestive and Liver Diseases,
University of Texas Southwestern
Method of DILIN in establishing causality [PDF]

Drug induced liver injury (DILI) represents one of the most serious adverse reactions due to drugs. The diagnosis of DILI requires a high level of suspicion and, indeed, is often overlooked. In essentially all settings, the diagnosis is one of exclusion. Evidence for or against a drug is often obtained retrospectively and is thus often inconclusive.

In an effort to better ascertain the causality of a particular drug in DILI, a number of different causality assessment tools have been developed. One of the first, and most prominent instruments is the RUCAM, developed in 1990, under the auspices of the Council for International Organizations of Medical Sciences (CIOMS), by a working group of expert hepatologists. Although this scale is felt to yield a valid assessment of hepatotoxicity, it is complex, and therefore is also believed to be difficult to use clinical practice. Another, somewhat simpler method developed and tested by Maria and Victorino is the M&V instrument. However, this tool has also failed to gain widespread appeal.
Because causality assessment in DILI is such a critical issue, and because the currently available instruments for guiding causality are believed to be suboptimal, a major effort of the DILI Network (DILIN) has been to attempt to improve the causality process.

The talk will focus on the general aspects of the causality process, highlight potential pitfalls of the RUCAM instrument, and point to potential new processes being discussed by DILIN.


  1. Report of an International Consensus Meeting. Criteria of drug-induced liver disorders. J Hepatol 1990;11:272-276.
  2. Danan G, Bénichou C. Causality assessment of adverse reactions to drugs. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993;46:1323-1330.
  3. Maria VAJ, Victorino RMM. Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis. Hepatology 1997;26: 664-669.

Biographical Sketch

Don was educated at the Virginia Polytechnical Institute (B.S., 1980) and the Medical College of Virginia at Richmond (M.D., 1984), after which he served as an internal medical resident at the University of California at San Francisco (1984-8). He followed with a fellowship in gastroenterology at UCSF (1988-92), and was chosen for staff positions there as a clinical instructor and attending physician (1992-5), assistant professor of medicine (1995-6). He then moved to Duke University as associate professor of medicine and Director of Hepatology at the Duke Liver Center (1997-2002). He was promoted to professor of medicine at Duke (2002-5), and then moved to the University of Texas Southwestern at Dallas TX as Professor of Medicine and Director, Digestive Diseases and Liver Division in late 2005.

During this time he received many awards (summa cum laude 1980; A.H. Strauss award for academic excellence, 1982; Alpha Omega Alpha, 1983; A.D. Williams award for being top student in junior clerkship and the Merck award for academic excellence, 1983; the William Branch award as top student in internal medicine and Herman Hertzberg award for excellence in service and scholarship, 1984; the American Gastroenterological Association senior fellow award, 1990, and its industry award, 1992; the World Congress of Gastroenterology young scholar award, 1994; Glaxo Institute of Digestive Health research award, 1995; Miles and Shirley Fiterman basic researcg award 1996; Burroughs Wellcome clinical scientist research award, 2000; and was elected to the American Society of Clinical Investigation, 2001.