Background & Aims: Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies. Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-α (TNF-α) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF-α-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis. Methods: Forty-eight patients with moderate to severe alcoholic hepatitis (Model for End-Stage Liver Disease score ≥15) were enrolled and randomized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks. Primary study end points included mortality at 1- and 6-month time points. Results: There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age, gender, and Model for End-Stage Liver Disease score. The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis (22.7% vs 36.4%, respectively; OR, 1.8; 95% CI, 0.5-6.5). The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group (57.7% vs 22.7%, respectively; OR, 4.6; 95% CI, 1.3-16.4; P = .017). Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group (34.6% vs 9.1%, respectively, P = .04). Conclusions: In patients with moderate to severe alcoholic hepatitis, etanercept was associated with a significantly higher mortality rate after 6 months, indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis.
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