Erythropoietin and Cytokine Levels in the Anemia of Severe Alcoholic Liver Disease

Purpose : The anemia of chronic disease is mediated by the cytokines that modulate the immune response, such as tumor necrosis factor (TNF) and γ-interferon (γ-IFN), and is associated with a blunted serum erythropoietin (sEPO) response to anemia. Previous reports suggest that patients with liver disease (LD) also exhibit a blunted sEPO response to anemia, and that patients with alcoholic LD had altered cytokines, including elevated TNF levels. To investigate the pathogenesis of anemia in alcoholic LD, sEPO, TNF, and γ-IFN levels were determined in patients who had participated in a Department of Veterans Affairs Cooperative study of alcoholic LD. Methods : sEPO, serum TNF-α, and serum γ-IFN levels were evaluated in 40 patients with severe biopsy-proven alcoholic LD whose serum had been stored during the Department of Veterans Affairs Cooperative Study 275, and in 18 patients with iron deficiency (controls). Results : Mean hemoglobin (Hgb) was 11.2 ± 0.3 g/dl for LD patients versus 11.4 ± 0.4 g/dl for controls ( p = 0.84). sEPO levels measured by ELISA were 29.6 ± 4.1 units/liter in LD patients versus 25.4 ± 5.4 units/liter in controls ( p = 0.64). In both sets of patients, sEPO and Hgb were inversely related; the slopes of the two regression lines did not differ significantly ( p = 0.92). TNF was detected in 3 of 40 LD patients and in 0 of 18 iron-deficient patients. Detection of TNF did not correlate with sEPO or Hgb, but did correlate strongly with severe caloric malnutrition (marasmus) and mortality at 6 months ( p = 0.049 and 0.04, respectively).γ-IFN was not detected. Conclusions : These findings indicate that the sEPO response is preserved in patients with severe alcoholic LD, and suggest that anemia in LD arises from different mechanisms than does the anemia of chronic disease. TNF production in severe alcoholic LD is strongly correlated with caloric malnutrition and mortality.