Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis

J Hepatol. 2004 Aug;41(2):229-34. doi: 10.1016/j.jhep.2004.04.028.

Abstract

Background/aims: In alcoholic hepatitis (AH), soluble TNF alpha receptor-1 (sTNF-R1) is increased. Elevated TNF alpha predicts mortality, but infection influences TNF alpha values. In patients with AH, we determined the prognostic value of TNF alpha, sTNF-R1, and lipopolysaccharide binding protein (LBP) and CD14, both involved in endotoxemia-associated inflammation.

Methods: One hundred and eight cirrhotic patients (Pugh score 10 [6-13]) and biopsy-proven AH (Maddrey's DF <32: n=46; > or =32: n=62) without associated infection were included within 8 days of admission and followed-up for 3 months. Cytokines were measured using specific immunoassays. Patients with severe AH received steroids.

Results: Twenty four patients died at a median time of 35 days (range: 3-89). The overall survival was 78%. Multivariate Cox regression analysis showed that sTNF-R1 was an independent predictor of mortality, (OR 4.33: 95% CI [1.12-16.75]). Pugh's score (P=0.618), Maddrey's DF (P=0.182), creatinine (P=0.197), TNF alpha (P=0.319), LBP (P=0.362), and CD14 (P=0.347) were not related to survival.

Conclusions: In patients with AH, sTNF-R1 measured at admission is an independent predictor of survival at 3 months. Provided that TNF-R1 mediates the cytotoxic actions of TNFalpha, these results support the concept of dysregulated TNF alpha metabolism in AH.

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking
  • Female
  • Hepatitis, Alcoholic / blood*
  • Hepatitis, Alcoholic / mortality*
  • Hepatitis, Alcoholic / psychology
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Receptors, Tumor Necrosis Factor, Type I / blood*
  • Receptors, Tumor Necrosis Factor, Type I / chemistry
  • Regression Analysis
  • Solubility
  • Survival Analysis
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha