Experimental data suggest that somatostatin is metabolized by both liver and kidneys. Results in humans are conflicting. By studying a group of cirrhotic patients with surgically induced end-to-side portacaval shunts, basally and during a somatostatin infusion, we have been able to analyze separately the hepatic and splanchnic metabolism of this peptide. After catheterization, samples were obtained from the pulmonary artery, portal and hepatic veins. Basal pulmonary artery immunoreactive somatostatin (IRS) was significantly higher (p < 0.001) in the cirrhotic patients (96 ± 11 pg per ml) than in a sex- and age-matched control group (31.4 ± 5.8 pg per ml). During the infusion of exogenous somatostatin, HiS values were higher in arterial (12,269 ± 1, 198 pg per ml) than in hepatic venous blood (7,648 ± 1,234 pg per ml), indicating hepatic extraction of the peptide; but there was also a substantial splanchnic extraction demonstrated by higher arterial (12,269 ± 1,532 pg per ml) than portal values (6,754 ± 1,040 pg per ml) of IRS.

During the somatostatin infusion, at very high circulation IRS levels, the liver was able to extract 38% of the peptide. This suggests that the high basal IRS levels found in liver cirrhosis are not likely to be due to hepatic failure. Possible mechanisms may involve increased somatostatin secretion, predominance of high molecular weight moieties of IRS which may not be as effectively removed by the liver, and/or portal-systemic shunting.