A Pilot Study of the Safety and Tolerability of Etanercept in Patients with Alcoholic Hepatitis

K. V Narayanan Menon, Linda Stadheim, Patrick Sequeira Kamath, Russell H. Wiesner, Gregory James Gores, Craig J. Peine, Vijay Shah

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)255-260
Number of pages6
JournalAmerican Journal of Gastroenterology
Volume99
Issue number2
DOIs
StatePublished - Feb 2004

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Alcoholic Hepatitis
Safety
Tumor Necrosis Factor-alpha
Hepatic Encephalopathy
Tumor Necrosis Factor Receptors
Etanercept
Interleukin-6
Survival Rate
Hemorrhage
Cytokines
Morbidity
Mortality
Therapeutics
Infection

ASJC Scopus subject areas

  • Gastroenterology

Cite this

A Pilot Study of the Safety and Tolerability of Etanercept in Patients with Alcoholic Hepatitis. / Menon, K. V Narayanan; Stadheim, Linda; Kamath, Patrick Sequeira; Wiesner, Russell H.; Gores, Gregory James; Peine, Craig J.; Shah, Vijay.

In: American Journal of Gastroenterology, Vol. 99, No. 2, 02.2004, p. 255-260.

Research output: Contribution to journalArticle

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