Prostaglandin production in cirrhosis and portal hypertension—Experimental and clinical study

Abstract

Disease-related changes in prostaglandin (PG) levels may contribute to a bleeding tendency and local vasodilation in the portal circulation in patients with liver cirrhosis. We measured the plasma and tissue PG metabolite levels (6-keto PGF1 α and thromboxane TXB 2) in the systemic and portal circulation in 12 rats with CCl 4-induced liver cirrhosis (LC rats) and ten with portal hypertension induced by 2 weeks of partial portal ligation (PH rats) and compared them with normal control rats ( n=10). We also compared the plasma PG metabolite levels in the systemic and portal circulations in 11 cirrhotic patients with hepatocellular carcinoma (HCC) and five patient controls without liver disease. In the animal study, LC rats had significantly higher portal blood 6-keto PGF1 α ( P<0.01) and TXB 2 ( P<0.05) levels than the control rats; and significantly higher systemic blood TXB 2 level than PH rats ( P<0.05) and control rats ( P<0.05), but the systemic blood 6-keto PGF1 α levels were not significantly different among the three groups. PH and LC rats had significantly higher portal vein tissue 6-keto PGF1 α levels than the control rats ( P<0.01 and P<0.05), and the level in PH rats was higher than that in LC rats ( P<0.05). LC rats had significantly higher portal vein tissue TXB 2 level than control rats ( P<0.05). The liver tissue levels of both metabolites did not differ among the three groups. Compared with control rats, LC rats had significantly higher 6-keto PGF1 α/TXB 2 ratios in the portal circulation ( P<0.01) and liver tissue ( P<0.05); and PH rats had significantly higher ratios in the portal vein ( P<0.01), systemic circulation ( P<0.05) and liver tissue ( P<0.05). In the clinical study, both PG metabolite levels were significantly higher in the portal circulation than in the systemic circulation in cirrhotic patients with HCC, whereas the levels were only slightly higher in the portal circulation in control patient without liver disease. The PG metabolite ratio was significantly higher in the portal circulation than in the systemic circulation in cirrhotic patients (2.0±0.1 vs. 1.5±0.1, P<0.05), but the ratios were not significantly different in patient controls (1.8±0.3 vs. 1.3±0.1). These results suggest that the production of PG, especially of prostacycline, may be enhanced in the portal system in cirrhosis and may in part evoke portal pressure increase and other vascular alterations.