Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis.
OBJECTIVE
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.
Spahr
Laurent
L
Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland. laurent.spahr@hcuge.ch
Giostra
Emile
E
Frossard
Jean-Louis
JL
Bresson-Hadni
Solange
S
Rubbia-Brandt
Laura
L
Hadengue
Antoine
A
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D005260:Female; D006519:Hepatitis, Alcoholic / Q000097:blood* / Q000401:mortality* / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood* / Q000737:chemistry; D012044:Regression Analysis; D012995:Solubility; D016019:Survival Analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha