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J Hepatol. 2003 Apr;38(4):419-25.

Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis.

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  • 1Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. herbert.tilg@uibk.ac.at

Abstract

BACKGROUND/AIMS:

Severe alcoholic hepatitis (AH) is associated with high mortality. Tumor necrosis factor-alpha (TNFalpha) has been demonstrated to play an important role in its pathophysiology.

METHODS:

Twelve patients with biopsy-confirmed AH and a Maddrey discriminant factor >32 were treated with a single infusion of the anti-TNF monoclonal antibody Infliximab at a dose of 5mg/kg body weight. Serial measurements were made for various cytokines using specific enzyme-linked immunoassays (ELISA). In four patients, liver biopsy samples were available pretreatment and on day+28 of therapy.

RESULTS:

Ten of the 12 patients are alive at a median of 15 (12-20) months. Two patients died within 30 days from septicemia. Serum bilirubin levels, Maddrey score, neutrophil count and C-reactive protein fell significantly within the first month. There was an early, though not significant, decrease in plasma levels of proinflammatory cytokines (interleukins (IL)-1beta, IL-6, IL-8, interferon-gamma), whereas plasma levels of TNFalpha remained near the sensitivity limit of the assay throughout the treatment course. While TNFalpha mRNA expression in the liver did not change, expression of IL-8, a cytokine regulated mainly by TNFalpha, was almost absent on day+28.

CONCLUSIONS:

Our data suggest that randomized controlled trials of anti-TNF antibody in severe AH are warranted.

PMID:
12663232
[PubMed - indexed for MEDLINE]
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