TY - JOUR
T1 - A Pilot Study of the Safety and Tolerability of Etanercept in Patients with Alcoholic Hepatitis
AU - Menon, K. V.Narayanan
AU - Stadheim, Linda
AU - Kamath, Patrick S.
AU - Wiesner, Russell H.
AU - Gores, Gregory J.
AU - Peine, Craig J.
AU - Shah, Vijay
PY - 2004/2
Y1 - 2004/2
N2 - BACKGROUND: Alcoholic hepatitis is a cause of major morbidity and mortality, and effective therapeutic regimens to treat this condition are lacking. Both experimental and clinical evidence indicates that tumor necrosis factor alpha (TNF), and the downstream cytokine interleukin-6 (IL-6), correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis, thereby implicating a possible role for inhibition of TNF in the treatment of alcoholic hepatitis. OBJECTIVE: The aim of the current study was to assess the safety and tolerability of a p75-soluble TNF receptor:FC fusion protein (etanercept), an agent that binds and neutralizes soluble TNF in patients with alcoholic hepatitis in the form of an open-label pilot trial. METHODS: Etanercept administration was targeted for 2 wk duration in 13 patients with moderate or severe alcoholic hepatitis as assessed by a discriminant function value greater than 15 and/or the presence of spontaneous hepatic encephalopathy. RESULTS: On an intention-to-treat basis, the 30-day survival rate of patients receiving etanercept was 92% (12/13). Adverse events that were encountered included infection, hepatorenal decompensation, and GI bleeding, which required premature discontinuation of etanercept in 23% of patients (3/13). CONCLUSIONS: This is the first study to examine TNF inhibition with etanercept in patients with alcoholic hepatitis and the results of this study support the rationale for larger controlled studies to further assess safety and efficacy.
AB - BACKGROUND: Alcoholic hepatitis is a cause of major morbidity and mortality, and effective therapeutic regimens to treat this condition are lacking. Both experimental and clinical evidence indicates that tumor necrosis factor alpha (TNF), and the downstream cytokine interleukin-6 (IL-6), correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis, thereby implicating a possible role for inhibition of TNF in the treatment of alcoholic hepatitis. OBJECTIVE: The aim of the current study was to assess the safety and tolerability of a p75-soluble TNF receptor:FC fusion protein (etanercept), an agent that binds and neutralizes soluble TNF in patients with alcoholic hepatitis in the form of an open-label pilot trial. METHODS: Etanercept administration was targeted for 2 wk duration in 13 patients with moderate or severe alcoholic hepatitis as assessed by a discriminant function value greater than 15 and/or the presence of spontaneous hepatic encephalopathy. RESULTS: On an intention-to-treat basis, the 30-day survival rate of patients receiving etanercept was 92% (12/13). Adverse events that were encountered included infection, hepatorenal decompensation, and GI bleeding, which required premature discontinuation of etanercept in 23% of patients (3/13). CONCLUSIONS: This is the first study to examine TNF inhibition with etanercept in patients with alcoholic hepatitis and the results of this study support the rationale for larger controlled studies to further assess safety and efficacy.
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U2 - 10.1111/j.1572-0241.2004.04034.x
DO - 10.1111/j.1572-0241.2004.04034.x
M3 - Article
C2 - 15046213
AN - SCOPUS:1442301516
SN - 0002-9270
VL - 99
SP - 255
EP - 260
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 2
ER -