AASLD-FDA-NIH-PhRMA- Hepatotoxicity Special Interest Group Meeting, 2007 Presentations

Issues and Controversies in DILI
(DILI = drug-induced liver injury)

• John Senior (FDA), Welcome

Session I: FDA Concept Paper: Premarketing Evaluation of DILI (Moderator – Paul Watkins, M.D., UNC, DILIN)

How can we best find and study DILI in clinical trials?

• Ruyi He, M.D., FDA, Drafting of concept paper: Premarketing Evaluation of DILI
• John Senior, M.D., FDA, Rationale for concept paper and proposed guidance
• Jerry Stern, M.D., Boehringer Ingelheim, Commentary on concept paper
• Deborah Kirby, M.D., Pfizer, Commentary on concept paper
• Neil Kaplowitz, M.D., USC, AASLD commentary
• Paul Watkins, M.D., NIH, NIH/DILIN commentary
• Larry Lesko, Ph.D., FDA, Is the susceptibility to DILI in the genome?
• T. Andersson, Ph.D., AstraZeneca, Potential mechanisms of ximelagatran hepatotoxicity
• Janet Woodcock, M.D., FDA, Combining research with clinical study without regulatory penalty
• Session I: Summary of discussion, questions and answers [PDF 210KB]

Session II: Does Preexisting Liver Disease Make DILI More Likely? (Moderator – Neil Kaplowitz, M.D., USC)

Does liver disease increase chances of getting DILI?

• Robert Temple, M.D., FDA, No.
• Hari Mehendale, Ph.D., U LA, Yes.
• James H. Lewis, M.D., Georgetown, No.
• William M. Lee, M.D., UTSW, Yes.
• Rebecca Taub, M.D., Roche, Mechanisms of hepatic repair and regeneration in DILI
• Mark Avigan, M.D., FDA, Clinical evidence that it’s the patient, not the drug
• Robert Fontana, M.D, U MI, Putting it all together
• Session II: Summary of discussion, questions and answers [PDF 105KB]

Session III: Role of the Immune System in DILI, (Moderator – Holly A. Read, M.D., Abbott)

Why the variable latent period between exposure and onset of DILI?

• Jack Uetrecht, Ph.D., University of Toronto, Immune system mechanisms
• Neil Kaplowitz, M.D., USC, Non-immune mechanisms
• John Vierling, M.D., Baylor, Autoimmune hepatitis and drugs
• Leonard Seeff, M.D., NIH, Drugs that appeared to cause AIH
• Herb Bonkovsky, M.D., UCT, Can drugs cause or aggravate or uncover AIH?
• Session III: Summary of discussion, questions and answers [PDF 216KB]

Contact list for Authors.