ERYTHROPOIETIN AND CYTOKINE LEVELS IN THE ANEMIA OF SEVERE ALCOHOLIC LIVER-DISEASE

Purpose: The anemia of chronic disease is mediated by the cytokines th at modulate the immune response, such as tumor necrosis factor (TNF) a nd gamma-interferon (gamma-IFN), and is associated with a blunted seru m erythropoietin (sEPO) response to anemia. Previous reports suggest t hat patients with liver disease (LD) also exhibit a blunted sEPO respo nse to anemia, and that patients with alcoholic LD had altered cytokin es, including elevated TNF levels. To investigate the pathogenesis of anemia in alcoholic LD, sEPO, TNF, and gamma-IFN levels were determine d in patients who had participated in a Department of Veterans Affairs Cooperative study of alcoholic LD. Methods: sEPO, serum TNF-alpha, an d serum gamma-IFN levels were evaluated in 40 patients with severe bio psy-proven alcoholic LD whose serum had been stored during the Departm ent 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). I n both sets of patients, sEPO and Hgb were inversely related; the slop es 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-deficien t patients. Detection of TNF did not correlate with sEPO or Hgb, but d id correlate strongly with severe caloric malnutrition (marasmus) and mortality at 6 months (p = 0.049 and 0.04, respectively). gamma-IFN wa s not detected. Conclusions: These findings indicate that the sEPO res ponse is preserved in patients with severe alcoholic LD, and suggest t hat 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.