(Taken from application) The present proposal is for a planning grant to establish a multi-center United States-based study group for the clinical and basic investigation of all aspects of acute liver failure. This dramatic and devastating condition affects approximately 2,000 persons annually in the United States, developing when the sudden loss of liver cell function from a variety of causes leads to multi-organ failure with an 80% mortality. Even with the advent of liver transplantation, most patients die of their disease. Better understanding of the pathogenesis of acute liver failure would aid in its management, and preclude the need for liver transplantation. A multi-center approach would permit the collection of clinical information concerning pathogenesis and natural history, make available clinical samples for laboratory evaluation, and facilitate important therapeutic trials. Among the candidate therapies presently available are intravenous N-acetylcysteine and extracorporeal liver assist devices.
Our aim i s to establish the groundwork for a multi-center group involving 13 sites, so that future studies in acute liver failure may be performed. The planning study will be conducted in three phases: a development phase in which the database forms and interrelational mechanism is set in place, a data collection phase in which accrual of prospective data for one year will test the group's ability to gather information and clinical samples, and a third phase in which a pilot study of the use of N-acetylcysteine for treatment of acute liver failure not related to acetaminophen will be conducted. This planning grant will allow time for the group to be fully established prior to application for an RO1 grant for a full scale randomized, double-blind, controlled N-acetylcysteine study.
| Strnad, Pavel; Zhou, Qin; Hanada, Shinichiro et al. (2010) Keratin variants predispose to acute liver failure and adverse outcome: race and ethnic associations. Gastroenterology 139:828-35, 835.e1-3 |
| Lee, William M; Hynan, Linda S; Rossaro, Lorenzo et al. (2009) Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 137:856-64, 864.e1 |
| Lee, W M; Brown, K E; Young, N S et al. (2006) Brief report: no evidence for parvovirus B19 or hepatitis E virus as a cause of acute liver failure. Dig Dis Sci 51:1712-5 |
| Schiodt, Frank V; Rossaro, Lorenzo; Stravitz, Richard T et al. (2005) Gc-globulin and prognosis in acute liver failure. Liver Transpl 11:1223-7 |
| Larson, Anne M; Polson, Julie; Fontana, Robert J et al. (2005) Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 42:1364-72 |
| Schiodt, Frank Vinholt; Davern, Timothy J; Shakil, A Obaid et al. (2003) Viral hepatitis-related acute liver failure. Am J Gastroenterol 98:448-53 |
| Schiodt, Frank Vinholt; Lee, William M (2003) Fulminant liver disease. Clin Liver Dis 7:331-49, vi |
| Schiodt, Frank V; Balko, Jody; Schilsky, Michael et al. (2003) Thrombopoietin in acute liver failure. Hepatology 37:558-61 |
| Ostapowicz, George; Fontana, Robert J; Schiodt, Frank V et al. (2002) Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 137:947-54 |
| Reinus, J F; Persky, S; Burkiewicz, J S et al. (2000) Severe liver injury after treatment with the leukotriene receptor antagonist zafirlukast. Ann Intern Med 133:964-8 |
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