The Acute Liver Failure Study Group (ALFSG) was developed on the premise that a network of sites acting in concert was the only way to impact this rare condition by providing enough patients for detailed study and clinical trials. Since 1998, the group has collected and disseminated important clinical information and bio- samples on more than 1,600 patients and conducted a randomized controlled trial of N-acetylcysteine for non-acetaminophen acute liver failure (ALF). Among its accomplishments, ALFSG has provided new insights into the central role of acetaminophen (APAP) in ALF in United States patients and further characterized many of the other etiologies such as hepatitis A, hepatitis B, autoimmune hepatitis and ischemic liver disease as well as focusing on disease outcomes and the role of transplantation. More than 70 ancillary studies have been initiated utilizing our data and bio-samples, generating 37 original articles on all aspects of ALF. A recent addition was the Acute Liver Injury (ALI) study, capturing earlier stage disease, prior to the onset of advanced liver failure. Our plan for the future rests on our ability to continue the ALF registry while simultaneously addressing more basic mechanistic studies and performing additional therapy trials. Recent innovations within the group that will impact our functioning in the future include reducing the number of sites to our top participating centers, adopting electronic data capture and the collection of more detailed clinical information on our cases. Planned approaches for the future include more deliberate studies of genomics, cytokines, coagulation and hepatic regeneration, as well as the conduct of at least two clinical trials of new agents for treatment of this dreaded condition.

Public Health Relevance

Acute liver failure affects 2000 Americans annually, is sudden and often fatal. It is the most severe form of liver disease recognized, results from multiple causes (drugs or viruses) and sometimes requires liver transplantation for survival. The Acute Liver Failure Study Group is poised to improve understanding and provide new therapies to arrest the liver damage, avoid transplantation where possible, and save lives.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK058369-15
Application #
8731861
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Sherker, Averell H
Project Start
2000-09-01
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
15
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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
Davis, Brian C; Tillman, Holly; Chung, Raymond T et al. (2017) Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group. Liver Int 37:509-513
Cardoso, Filipe S; Gottfried, Michelle; Tujios, Shannan et al. (2017) Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology :
Rubin, Jessica B; Hameed, Bilal; Gottfried, Michelle et al. (2017) Acetaminophen-induced Acute Liver Failure is More Common and More Severe in Women. Clin Gastroenterol Hepatol :
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
Karvellas, Constantine J; Cardoso, Filipe S; Gottfried, Michelle et al. (2017) HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death. Clin Gastroenterol Hepatol 15:113-122
Stravitz, R Todd; Gottfried, Michelle; Durkalski, Valerie et al. (2017) Safety, Tolerability and Pharmacokinetics of L-Ornithine Phenylacetate in Patients with Acute Liver Injury/Failure and Hyperammonemia. Hepatology :
Lee, William M (2017) Acetaminophen (APAP) hepatotoxicity-Isn't it time for APAP to go away? J Hepatol 67:1324-1331
Koch, David G; Speiser, J L; Durkalski, V et al. (2017) The Natural History of Severe Acute Liver Injury. Am J Gastroenterol 112:1389-1396

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