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 #
5U01DK058369-13
Application #
8330880
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (O2))
Program Officer
Sherker, Averell H
Project Start
2000-09-01
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
13
Fiscal Year
2012
Total Cost
$2,500,000
Indirect Cost
$372,433
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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Dubin, Perry H; Yuan, Hejun; Devine, Robert K et al. (2014) Micro-RNA-122 levels in acute liver failure and chronic hepatitis C. J Med Virol 86:1507-14
Karkhanis, Jamuna; Verna, Elizabeth C; Chang, Matthew S et al. (2014) Steroid use in acute liver failure. Hepatology 59:612-21
Court, Michael H; Peter, Inga; Hazarika, Suwagmani et al. (2014) Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure. Drug Metab Dispos 42:28-32
Karvellas, Constantine J; Cavazos, Jorge; Battenhouse, Holly et al. (2014) Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study. Clin Gastroenterol Hepatol 12:1942-9.e1
McGill, Mitchell R; Staggs, Vincent S; Sharpe, Matthew R et al. (2014) Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome. Hepatology 60:1336-45
Karvellas, Constantine J; Fix, Oren K; Battenhouse, Holly et al. (2014) Outcomes and complications of intracranial pressure monitoring in acute liver failure: a retrospective cohort study. Crit Care Med 42:1157-67
Long, Dustin; Fix, Oren K; Deng, Xutao et al. (2014) Whole genome sequencing to identify host genetic risk factors for severe outcomes of hepatitis a virus infection. J Med Virol 86:1661-8
Mellinger, Jessica L; Rossaro, Lorenzo; Naugler, Willscott E et al. (2014) Epstein-Barr virus (EBV) related acute liver failure: a case series from the US Acute Liver Failure Study Group. Dig Dis Sci 59:1630-7
Metushi, Imir G; Sanders, Corron; Acute Liver Study Group et al. (2014) Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure. Hepatology 59:1084-93

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