HEPATIC RELEASE OF ERYTHROPOIETIN-INDUCED BY TRANSARTERIAL CHEMOEMBOLIZATION IN PATIENTS WITH HEPATOCELLULAR-CARCINOMA

It has been shown previously that erythropoietin expression in vitro b y hepatoma cells increases in response to hypoxia. To verify whether h ypoxia of the tumor might result in hepatic release of erythropoietin in vivo serum erythropoietin concentrations were measured immunoenzyma tically in 12 patients (5 women, 7 men) who underwent transarterial ch emoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in thr ee male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization o f the hepatic veins and of the right antecubital vein. None of the pat ients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 mu g/L, serum erythropoietin concentrations wer e the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t -test). The ratio of hepatic vein/antecubital vein serum erythropoieti n concentrations increased from 0.85 at baseline to 1.30 at +2 days, p aralleling the increase of aspartate transaminase (r = .914, P < .005) . After chemoembolization, no correlation was found between serum eryt hropoietin and alpha-1-fetoprotein concentrations. The concentration o f the latter, stable initially, decreased 7 days after the procedure. These findings demonstrate that in patients with hepatocellular carcin oma hepatic release of erythropoietin can occur not only for unregulat ed paraneoplastic production by tumor cells but also as a predictable response to local hypoxia in the liver.