Soluble TNF-R1, but not TNF$alpha;, predicts the 3-month mortality in patients with alcoholic hepatitis*1

Abstract

Background/Aims In alcoholic hepatitis (AH), soluble TNFα receptor-1 (sTNF-R1) is increased. Elevated TNFα predicts mortality, but infection influences TNFα values. In patients with AH, we determined the prognostic value of TNFα, 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), TNFα (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 TNFα, these results support the concept of dysregulated TNFα metabolism in AH.