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

Background/Aims: In alcoholic hepatitis (AH), soluble TNFalpha receptor-1 (sTNF-R1) is increased. Elevated TNFalpha predicts mortality, but infection influences TNFalpha values. In patients with AH, we determined the prognostic value of TNFalpha, 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; = 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), TNFalpha (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 TNFalpha metabolism in AH. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.