title: A pilot study of the safety and tolerability of etanercept in patients with alcoholic hepatitis.
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
  
  
  
  CONCLUSIONS
  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). 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.
authors.affiliation: Advanced Liver Disease Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: K V Narayanan
authors.initials: KV
authors.lastname: Menon
authors.forename: Linda
authors.initials: L
authors.lastname: Stadheim
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Kamath
authors.forename: Russell H
authors.initials: RH
authors.lastname: Wiesner
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Peine
authors.forename: Vijay
authors.initials: V
authors.lastname: Shah
mesh_terms: D000328:Adult; D000368:Aged; D000068800:Etanercept; D005260:Female; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept