Effect of chronic treatment with nadolol plus isosorbide-5-mononitrate on liver blood flow and liver metabolic activity in cirrhosis

The aim of the study was to assess the long-term effect of the addition of long-acting nitrates to beta-blockers on liver blood flow and liver metabolic activity in patients with cirrhosis and portal hypertension. Eleven patients with cirrhosis and portal hypertension were investigated by hepatic vein catheterization and KG constant infusion in baseline conditions, after one month of chronic treatment with nadolol, after 3 months of chronic treatment with nadolol plus isosorbide-S-mononitrate, and (in 7 cases) after one year of combined treatment. Hepatic venous pressure gradient (HVPG) decreased significantly after nadolol (p<.Ol), and more so after the addition of isosorbide-5mononitrate (p<.OOl). Hepatic blood flow, KG intrinsic hepatic clearance, and extraction ratio did not change significantly as an average, although few cases showed increase or decrease in either parameter. A significant correlation was found between changes in ICG intrinsic hepatic clearance and in HVPG (r=.62; p=.O4). In conclusion, liver blood flow and liver metabolic activity are not consistently affected by the addition of isosorbide-5-mononitrate to nadolol. Substantial decrease in ICG intrinsic hepatic clearance may occur in patients with marked decrease in portal pressure after combined treatment. SINUSOIDAL BUT NOT PREHEPATIC PORTAL PRESSURE IS ASSOCIATED WITH DECREASED HEPATIC NO SYNTHASE (NOS) ACTIVITY.