Since 1998, the Acute Liver Failure Study Group (ALFSG) has provided a network of sites across the United States, dedicated to learning and disseminating new knowledge about acute liver failure, a super-orphan condition that frequently kills young people and involves high resource utilization, despite its rarity. Few, if any, treatments have become available to preserve liver function and avoid the dire consequences of the sudden loss of hepatocyte mass. ALFSG has collected and disseminated important clinical information and bio-samples on more than 2,500 patients and conducted a controlled trial of N-acetylcysteine and a safety trial of ornithine phenylacetate (OPA) as putative treatment options. In addition, 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 90 ancillary studies have been initiated utilizing our data and bio- samples, generating ~70 original articles on all aspects of ALF. With our realignment of sites in 2010 and subsequent addition of 4 more sites, enrollment has increased, and this will facilitate more rapid completion of forthcoming trials. The correct assessment of etiology and prognosis on admission are vital to the management of ALF. Our new initiatives are directed at strengthening our diagnostic and prognostic assessments with further testing via point-of-care assays: the acetaminophen adduct assay, a dynamic measure of hepatic mass (methacetin breath test), evaluation of the role of coagulation factors in the condition (utilizing the ROTEM thromboelastogram), and finally testing the efficacy of OPA as an ammonia-trapping agent to ameliorate encephalopathy and brain edema. Additional approaches will include careful analyses of causality, fine tuning of prognostic assessments and, possibly, and the possible introduction of a liver support machine in the latter part of the grant cycle. Continuing studies of genomics, cytokines, coagulation and hepatic regeneration, compliment the clinical work and continue to make ALFSG a landmark research network and resource for other investigators.

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 often 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 thus 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 #
5U01DK058369-19
Application #
9549042
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Sherker, Averell H
Project Start
2000-09-01
Project End
2020-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
19
Fiscal Year
2018
Total Cost
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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Kok, Beverley; Lester, Erica L W; Lee, William M et al. (2018) Acute Liver Failure from Tumor Necrosis Factor-? Antagonists: Report of Four Cases and Literature Review. Dig Dis Sci 63:1654-1666
Rubin, Jessica B; Hameed, Bilal; Gottfried, Michelle et al. (2018) Acetaminophen-induced Acute Liver Failure Is More Common and More Severe in Women. Clin Gastroenterol Hepatol 16:936-946
Stravitz, R Todd; Gottfried, Michelle; Durkalski, Valerie et al. (2018) Safety, tolerability, and pharmacokinetics of l-ornithine phenylacetate in patients with acute liver injury/failure and hyperammonemia. Hepatology 67:1003-1013
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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
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

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