Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis
2003; Elsevier BV; Volume: 38; Issue: 4 Linguagem: Inglês
10.1016/s0168-8278(02)00442-7
ISSN1600-0641
AutoresHerbert Tilg, Rajiv Jalan, Arthur Kaser, Nathan Davies, Felix Offner, Stephen Hodges, Othmar Ludwiczek, Debbie L. Shawcross, Heinz Zoller, Akeel Alisa, Rajeshwar P. Mookerjee, Ivo Graziadei, Christian Datz, Michael Trauner, Detlef Schuppan, Peter Obrist, Wolfgang Vogel, Roger Williams,
Tópico(s)Hepatitis C virus research
ResumoSevere alcoholic hepatitis (AH) is associated with high mortality. Tumor necrosis factor-alpha (TNFalpha) has been demonstrated to play an important role in its pathophysiology.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.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.Our data suggest that randomized controlled trials of anti-TNF antibody in severe AH are warranted.
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