Hepatic tissue endothelin-1 levels in chronic liver disease correlate withdisease severity and ascites

OBJECTIVES: Plasma endothelin-l (ET-1) levels are increased in patients wit h cirrhosis and ET-I production is increased in the liver itself during exp erimental injury. These data suggest a possible role for this vasoactive pe ptide in intrahepatic microcirculatory changes that contribute to the patho genesis of portal hyper-tension in cirrhosis. Therefore the aims of this st udy were to determine whether ET-1 levels were abnormal in the livers of pa tients with cirrhosis and to investigate possible clinical correlates of al tered hepatic ET-I in cirrhosis. METHODS: Liver specimens were obtained from explants at the time of liver t ransplantation in 62 cirrhotic patients; 49 without pretransplantation tran sjugular intrahepatic portosystemic shunt (TIPS) and 13 with pretransplanta tion TIPS. The presence of ascites was evaluated by physical examination an d ultrasonography. Control specimens consisted of livers with normal morpho logy obtained from patients who died from nonliver-related causes. Hepatic ET-1 was measured by enzyme immunoassay. RESULTS: Hepatic ET-1 levels in cirrhotics without (0.17 pg/mg liver tissue ) or with TIPS (0.12 pg/mg) were higher than in control patients [0.04 pg/m g (p = 0.02 for ET-1 levels in cirrhotics with or without TIPS vs control)] . In cirrhotics without ascites who had not had TIPS, ET-1 levels (0.07 pg/ mg [0.04-1.00]) were similar to those of the con trols. In contrast, ET-I c ontent was increased in cirrhotics with small(0.11 pg/mg; p = 0.0002) and m oderate-to-large (0.69 pg/mg; p = 0.0002) amounts of ascites compared to pa tients without ascites. There was a modest correlation between ET-1 levels and Child-Pugh score (correlation coefficient 0.32; p = 0.03) and ET-1 leve ls were significantly higher in patients with Child-Pugh score of 13 or gre ater (0.88 pg/mg; p = 0.02) than in those with Child-Pugh score of 12 or le ss (0.16 pg/mg). CONCLUSIONS: Hepatic tissue ET-I levels are increased in the liver of patie nts with cirrhosis. This increase appears to be proportional to the severit y of both liver disease and ascites. These data raise a possible role for E T-1 in modulation of intrahepatic resistance in cirrhotic portal hypertensi on. (Am J Gastroenterol (C) 2000 by Am. Cell. of Gastroenterology) 2000,95. 199-203.