Sign In

Also in this Section

How Should Liver Injury and Dysfunction Caused by Drugs Be Measured, Evaluated, and Acted Upon in Clinical Trials?

This meeting was held March 23-24, 2016

Clinical trials in humans exposed to new drugs being developed provide data for the regulatory decisions on approval or non-approval and provide the best information to guide optimal use after marketing by prescribers in treating patients. Speeding and optimizing new drug development during the investigational new drug (IND) period represents the greatest opportunity to shorten time and reduce costs from discovery to approval. There is urgent need to update and revise thinking to consider investigational treatment of patients with pre-existing liver diseases such as chronic viral infection with hepatitis C or B, alcoholic and non-alcoholic steatohepatitis, and other liver disorders. It is also important to recognize hepatocyte adaptation, and to reconsider if controlled rechallenge can be done safely in the carefully controlled environment of clinical trials. This conference will seek comments and proposals from industry, investigators, and regulators on these and other controversial issues that need to be faced, considered, debated, and if possible resolved toward reaching consensus.

Meeting Organizers: John Senior, Lana Pauls, Paul Watkins, Mark Avigan, John-Michael Sauer, Arie Regev
 

2016 Program Presentations

Presenter(s)

Meeting Agenda (pdf)

Session Transcripts

   Day 1 - Session I and II  (pdf)
   Day 2 - Session III and IV (pdf)

SESSION I Hepatocyte Adaptation and Possible Rechallenge
Moderators: Arie Regev and John Senior
Welcome (pdf)  

Rechallenge is too dangerous (pdf)
or PowerPoint notes version (pdf)

Christine Hunt
photo, biosketch, abstract (pdf)
Maybe it's not (pdf)
or PowerPoint notes version (pdf)
Vid Stanulovic
photo, biosketch, abstract (pdf)
It really is too dangerous (pdf)
or PowerPoint notes version (pdf)
Julie Papay
photo, biosketch, abstract (pdf)

The isoniazid story, one more time, with implications (pdf)
or PowerPoint notes version (pdf)

John Senior
photo, biosketch, abstract (pdf)
Discussion and Debate of Issues (pdf) ALL PRESENT
Interactions between drug properties and host factors (pdf)
or PowerPoint notes version (pdf)
Ayako Suzuki
photo, biosketch, abstract (pdf)
Mechanism of hepatocyte adaptation to chemical injury (pdf)
or PowerPoint notes version (pdf)
Neil Kaplowitz
photo, biosketch, abstract (pdf)
New data on adaptive processes (pdf)
or PowerPoint notes version (pdf)
Lily Dara
photo, biosketch, abstract (pdf)

Allergic DI++LI from suppression of myeloid cells (pdf)
or PowerPoint notes version (pdf)

Article citation
Chakraborty, M., Fullerton, A. M., Semple, K., Chea, L. S., Proctor, W. R.,
Bourdi, M., Kleiner, D. E., Zeng, X., Ryan, P. M., Dagur, P. K., Berkson, J. D.,
Reilly, T. P. and Pohl, L. R. (2015), Drug-induced allergic hepatitis develops
in mice when myeloid-derived suppressor cells are depleted prior to halothane
treatment. Hepatology, 62: 546-557. doi: 10.1002/hep.27764

Mala Chakraborty
photo, biosketch, abstract (pdf)
General Discussion of Issues (pdf) ALL PRESENT
SESSION II Treating Advanced Liver Disease with Drugs
Moderators: Debbie Birnkrant and Mark Avigan
Can study protocols protect patients with liver disease from serious DILI? (pdf)
or PowerPoint notes version (pdf)
John Vierling
photo, biosketch, abstract (pdf)
Best use of MELD/CTP scores for baseline and treatment assessment (pdf)
or PowerPoint notes version (pdf)
Patrick Kamath
photo, biosketch, abstract (pdf)
Liver function testing to assess treatment effects and predict outcome in HCVLD (pdf)
or PowerPoint notes version (pdf)
Greg Everson
photo, biosketch, abstract (pdf)
Acute hepatotoxicity in HCV-cirrhotics treated with direct-acting antiviral agents (pdf)
or PowerPoint notes version (pdf)
Michael Fried
photo, biosketch, abstract (pdf)
General Discussion of Issues (pdf) ALL PRESENT
Can we test liver function to assess treatment effects and course of NASH? (pdf)
or PowerPoint notes version (pdf)
Arun Sanyal
photo, biosketch, abstract (pdf)
How can we recognize and manage DILI in patients with advanced NASH? (pdf)
or PowerPoint notes version (pdf)
Bob Fontana
photo, biosketch, abstract (pdf)
Clinical trial guidelines for DILI in patients which chronic liver disease (pdf)
or PowerPoint notes version (pdf)
Mark Avigan
photo, biosketch, abstract (pdf)
Recognizi/ng, assessing managing acute DILI in HCVLD - FDA challenges (pdf)
or PowerPoint notes version (pdf)
Poonam Mishra
photo, biosketch, abstract (pdf)
Recognizing, assessing managing acute DILI in NASH - FDA challenges (pdf)
or PowerPoint notes version (pdf)
Ruby Mehta
photo, biosketch, abstract (pdf)
General Discussion of Issues (pdf) ALL PRESENT
SESSION III Immune-mediated DILI Caused by Monoclonal Antibodies (mabs)
Moderators: John-Michael Sauer and Jack Uetrecht
Mechanisms of immune tolerance (pdf)
or PowerPoint notes version (pdf)
Amy Rosenberg
photo, biosketch, abstract (pdf)
DILI caused by anti-TNF agents Herb Bonkovsky
photo, biosketch, abstract (pdf)
Inhibition of immune tolerance unmasks DILI potential (pdf)
or PowerPoint notes version (pdf)
Jack Uetrecht
photo, biosketch, abstract (pdf)
General Discussion of Issues (pdf) ALL PRESENT
DILI caused by checkpoint inhibitors and other anti-cancer antibodies (pdf)
or PowerPoint notes version (pdf)
Cyril Konto
photo, biosketch, abstract (pdf)
DILI due to immunotherapy targeting immune checkpoints: how to treat? (pdf)
or PowerPoint notes version (pdf)
Arie Regev
photo, biosketch, abstract (pdf)
Monoclonal antibody-induced DILI --- a regulatory perspective (pdf)
or PowerPoint notes version (pdf)
Daniel Suzman
photo, biosketch, abstract (pdf)
General Discussion of Issues (pdf) ALL PRESENT
SESSION IV Hot new breakthrough findings and viewpoints
Moderators: Paul Watkins and Gyongyi Szabo
Is the eDISH program the long-sought and best current biomarker for DILI? (pdf)
or PowerPoint notes version (pdf)
John Senior
photo, biosketch, abstract (pdf)
Transformative DILI biomarkers - DILIN/SAFE-T collaboration (pdf)
or PowerPoint notes version (pdf)
Rachel Church
photo, biosketch, abstract (pdf)
Application of novel biomarkers to assess liver safety in clinical trials (pdf)
or PowerPoint notes version (pdf)
Paul Watkins
photo, biosketch, abstract (pdf)
Targeting HMGB1 with antibodies and inhibitory peptides (pdf)
or PowerPoint notes version (pdf)
Dan Antoine
photo, biosketch, abstract (pdf)
General Discussion of Issues (pdf) ALL PRESENT
Liver disease among infants receiving parenteral nutrition (pdf)
or PowerPoint notes version (pdf)
Katherine Gura
photo, biosketch, abstract (pdf)
TAK-875 (fasiglifam) - the real story (pdf)
or PowerPoint notes version (pdf)
Yvonne Dragan
photo, biosketch, abstract (pdf)
Modelling drug-induced lipotoxicity (pdf)
or PowerPoint notes version (pdf)
Scott Siler
photo, biosketch, abstract (pdf)
NCATS's liver-on-a chip (pdf)
or PowerPoint notes version (pdf)
Lans Taylor
photo, biosketch, abstract (pdf)
Role of exosomes in DILI and alcoholic hepatitis (pdf)
or PowerPoint notes version (pdf)
Gyongyi Szabo
photo, biosketch, abstract (pdf)
General Discussion of Issues (pdf) ALL PRESENT

Proceedings Archive

2015
2014
2013
2012
2011
2010
2009
2008-1999 (FDA website)

Save the date
Drug-Induced Liver Injury Annual Conference XVII
Jun 6-7, 2017
College Park Marriott
University of Maryland Conference Center