Severe alcoholic hepatitis (AH) is associated with high mortality. Tumor necrosis factor-alpha (TNF) plays an important role in its pathophysiology.
In this study, researchers from Europe assessed 12 patients with biopsy-confirmed AH and a Maddrey discriminant factor >32.
Patients were treated with a single infusion of the anti-TNF monoclonal antibody infliximab at a dose of 5mg per kg body weight.
The team made serial measurements for various cytokines using specific enzyme-linked immunoassays (ELISA).
|Serum bilirubin levels, Maddrey score, neutrophil count, and C-reactive protein fell within the first month.|
|Journal of Hepatology|
In 4 patients, liver biopsy samples were available pretreatment, as well as on day 28 of therapy.
The research team found that 10 of the 12 patients were alive at a median of 15 months. However, 2 patients died within 30 days from septicemia.
The team determined that serum bilirubin levels, Maddrey score, neutrophil count, and C-reactive protein fell significantly within the first month.
They identified an early decrease in plasma levels of proinflammatory cytokines (interleukins (IL)-1, IL-6, IL-8, interferon-gamma), but this was not significant.
Plasma levels of TNF remained near the sensitivity limit of the assay throughout the treatment course.
While TNF mRNA expression in the liver did not change, expression of IL-8, a cytokine regulated mainly by TNF, was almost absent on day 28.
Dr Tilg's team concluded, "Our data suggest that randomized controlled trials of anti-TNF antibody in severe AH are warranted".