Influence of probiotics an neutrophil function in alcoholic hepatitis

Alcoholic hepatitis is a life-threatening disease with a 1-year mortality of >50%. Patients with alcoholic hepatitis are known to be prone to bacterial infections. Possible mechanisms contributing to the increased risk of infection in patients with alcoholic hepatitis are an increased intestinal bacterial translocation (invasion of bacteria through the wall of the gut) and decreased cellular immune response. Neutrophils (a subgroup of white blood cells) in the blood of patients with alcoholic hepatitis are "primed" (activated) which should enable them to exhibit their full antimicrobial capacity. However, despite increased priming, neutrophil function is poor as demonstrated by impaired neutophil phagocytotic capacity. Priming may be induced by endotoxin (toxic parts of certain bacteria) which was shown to be elevated in the serum of patients with alcoholic hepatitis. Elevated serum endotoxin levels may be caused by intestinal bacterial translocation due to intestinal bacterial overgrowth and increased intestinal permeability (impaired barrier function of the gut). The proposed study is designed to test the effect of treatment with probiotics (viable microorganisms that alter the gut microflora and exert beneficial health effects) an neutrophil function in patients with alcoholic hepatitis. We hypothesize that gut flora manipulation by probiotics reduces intestinal bacterial translocation and serum endotoxin levels and thus counteracts inadequate neutrophil priming. Decreased neutrophil priming could restore neutrophil function and thereby reduce the risk of infection and possibly improve survival of patients with alcoholic hepatitis. The specific aim of the proposed study is to test the effect of a specific probiotic mixture or placebo on local and systemic neutrophil function in patients with alcoholic hepatitis. Tests for neutrophil priming state, neutrophil phagocytotic function, intestinal permeability, cytokine production and endotoxin levels will be carried out before and alter treatment with probiotics. lf the above mentioned hypothesis holds true, manipulation of gut flora by probiotics could provide an easy-to-apply and cost-effective component in the therapeutic strategy against alcoholic hepatitis.