Plasma Tumor Necrosis Factor α Predicts Decreased Long-Term Survival in Severe Alcoholic Hepatitis

Authors

  • Michael E. Felver MD,

    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville. Maryland; and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • Esteban Mezey MD,

    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville. Maryland; and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • Marielena McGuire BA,

    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville. Maryland; and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • Mack C. Mitchell MD,

    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville. Maryland; and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • H. Frank Herlong MD,

    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville. Maryland; and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • George A. Veech,

    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville. Maryland; and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • Richard L. Veech MD, DPhil

    Corresponding author
    1. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville. Maryland; and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • This work was supported in part by the United States-Spanish Joint Committee for Scientific and Technological Cooperation, National Institute on Alcohol Abuse and Alcoholism Grant AA 00626 and In-Patient Clinical Research Center, National Institutes of Health Grant 5MOI RR00035. G.A. Veech was supported during this study by a fellowship from the Foundation for Advanced Research in the Medical Sciences, Easton, Maryland.

Reprint requests: Dr. Richard L. Veech. Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, 12501 Washington Ave., Rockville, MD 20852.

Abstract

Plasma tumor necrosis factor α (TNF α), interleukin 1 α (IL-1α), and interleukin 1 β (IL-1β) were measured in plasma samples obtained from 23 patients with severe alcoholic hepatitis on admission and after 30 days of hospitalization. Over a 2-year follow-up period, 14 patients died at a mean time of 8 months following discharge. The presence of elevated plasma TNF α either at admission or discharge from the hospital was associated with death in 82% (14/17) of patients. By contrast absence of elevated plasma TNF α was associated with survival in 100% (6/6). The difference in survival with and without detectable plasma TNF α was significant at p= 0.0022. Plasma TNF α was not elevated in alcoholic patients without clinically apparent liver disease, with alcoholic cirrhosis, or in nonalcoholic healthy controls. Plasma IL-1a was also significantly increased in alcoholic hepatitis whereas IL-1β was not. Neither IL-1α nor β was correlated with outcome in the alcoholic hepatitis group. It is concluded that the presence of elevated plasma TNF α is a significant predictor of decreased long-term survival in patients with severe alcoholic hepatitis.

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