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

J Hepatol. 2003 Apr;38(4):419-25. doi: 10.1016/s0168-8278(02)00442-7.


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.

Publication types

  • Clinical Trial
  • Comment
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Female
  • Gastrointestinal Agents / administration & dosage*
  • Hepatitis, Alcoholic / drug therapy*
  • Hepatitis, Alcoholic / pathology
  • Humans
  • Infliximab
  • 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 & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics


  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Infliximab