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Selected Publication:
Tilg, H; Jalan, R; Kaser, A; Davies, NA; Offner, FA; Hodges, SJ; Ludwiczek, O; Shawcross, D; Zoller, H; Alisa, A; Mookerjee, RP; Graziadei, I; Datz, C; Trauner, M; Schuppan, D; Obrist, P; Vogel, W; Williams, R.
Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis.
J Hepatol. 2003; 38(4):419-425
Doi: 10.1016/S0168-8278(02)00442-7
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Trauner Michael
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- 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 5 mg/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. (C) 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Antibodies, Monoclonal - administration and dosage
- Female -
- Gastrointestinal Agents - administration and dosage
- Hepatitis, Alcoholic - drug therapy Hepatitis, Alcoholic - pathology
- Humans -
- Interferon-gamma - blood
- Interleukin-6 - blood
- Interleukin-8 - blood Interleukin-8 - genetics
- Liver - pathology Liver - physiology
- Male -
- Middle Aged -
- Pilot Projects -
- RNA, Messenger - analysis
- Severity of Illness Index -
- Tumor Necrosis Factor-alpha - antagonists and inhibitors Tumor Necrosis Factor-alpha - genetics
- Find related publications in this database (Keywords)
- cytokines
- tumor necrosis factor-alpha
- infliximab
- alcoholic hepatitis
- inflammation