? The Acute Liver Failure Study Group is now in its 7th year of operation, the final year of its current funding. A prospective registry program comprising 24 adult and 24 pediatric sites has collected detailed data, serum, tissue and DNA on more than 750 adults and 300 children with well-defined acute liver failure. Studies by the group have described the overall impact of various disease categories in acute liver failure, in particular that of acetaminophen, the role of viruses and acetaminophen in indeterminate cases, the impact of transplantation and sepsis in determining outcome, and the importance of prognostic factors for survival. The three specific aims of the original study have largely been met or exceeded. More than 30 ancillary studies have been performed using the data and biological materials available; 12 original articles have been published. A therapeutic trial of N-acetylcysteine for patients with acute liver failure not due to acetaminophen has exceeded 50% enrollment, with results still blinded at this time. We anticipate finishing the trial in the next 2-3 years with the addition of international sites. The present competing continuation proposal would extend the data, serum, tissue and DNA registry as an available resource for the next 5 years, and take our study of acute liver failure to a new level. Our new aims are to internationalize the study to provide global information from 8-10 sentinel sites on all continents, and to explore in more detailed fashion certain aspects of ALF: psychosocial aspects of acetaminophen toxicity, drug-induced liver injury pathogenesis focused on genetic polymorphisms and intensive care management and liver transplantation.
A final aim i s to provide the logistical support for new therapy initiatives, even while the MAC study is being completed. Using a wider, global network will provide surveillance against new infectious or toxic agents worldwide, facilitate more detailed studies in certain areas and permit faster accrual of new patients for future therapeutic trials in this rare but frequently fatal condition. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK058369-09
Application #
7486195
Study Section
Special Emphasis Panel (ZDK1-GRB-4 (M1))
Program Officer
Robuck, Patricia R
Project Start
2000-09-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
9
Fiscal Year
2008
Total Cost
$842,667
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Stravitz, R Todd; Ellerbe, Caitlyn; Durkalski, Valerie et al. (2018) Bleeding complications in acute liver failure. Hepatology 67:1931-1942
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Randesi, Matthew; Levran, Orna; Correa da Rosa, Joel et al. (2017) Association of Variants of Arginine Vasopressin and Arginine Vasopressin Receptor 1A With Severe Acetaminophen Liver Injury. Cell Mol Gastroenterol Hepatol 3:500-505
Karvellas, Constantine J; Speiser, Jaime L; Tremblay, Mélanie et al. (2017) Elevated FABP1 serum levels are associated with poorer survival in acetaminophen-induced acute liver failure. Hepatology 65:938-949
Roberts, Dean W; Lee, William M; Hinson, Jack A et al. (2017) An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure. Clin Gastroenterol Hepatol 15:555-562.e3
Lee, William M (2017) Acetaminophen (APAP) hepatotoxicity-Isn't it time for APAP to go away? J Hepatol 67:1324-1331

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