BACKGROUND:Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT).Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study aimed to measure serum ET levels in hospitalized cirrhotic patients and to determine their association with PPHT and patient outcome.METHODS:Fifty-seven cirrhotic patients [43 males;median age 58 (28-87) years] underwent Doppler echocardiography.Patients with systolic pulmonary arterial pressure ≥40 mmHg and pulmonary acceleration time <100 ms were deemed to have PPHT.ET-1,2,and 3 serum levels were measured with an ELISA assay.All-cause mortality was recorded over a median period of 24 months.RESULTS:Nine out of 57 patients (15.8%) had PPHT.Among various clinical variables,only autoimmune hepatitis was associated with PPHT (OR=11.5;95% CI,1.58-83.4;P=0.01).ET-1 levels [9.1 (1.6-20.7) vs 2.5 (1.4-9.2) pg/mL,P=0.02] and the ET-1/ET-3 ratio [4.73 (0.9-22.4) vs 1.6 (0.3-10.7),P=0.02] were significantly higher in patients with PPHT than in those without.ET-2 and ET-3 levels did not differ between the two groups.There was no difference in survival between the two groups,although ET-1 levels were associated with an adverse outcome in Cox regression analysis (HR=1.11;95% CI,1.02-1.22;P=0.02 per unit increase in ET-1).CONCLUSION:Our data suggest that ET-1 and the ET-1/ET-3 ratio are elevated in patients with PPHT and that ET-1 is associated with a poor outcome irrespective of PPHT. BACKGROUND: Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT) .Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study aimed to measure serum ET levels in hospitalized cirrhotic patients and to determine their association with PPHT and patient outcome. METHODS: Fifty-seven cirrhotic patients [43 males; median age 58 (28-87) years] underwent Doppler echocardiography. Patients with systolic pulmonary arterial pressure> 40 mmHg and pulmonary acceleration time <100 ms were deemed to have PPHT.ET-1, 2, and 3 serum levels were measured with an ELISA assay. All-cause mortality was recorded over a median period of 24 months .RESULTS: Nine out of 57 patients (15.8%) had PPHT.Among various clinical (P <0.01). Effusion, only autoimmune hepatitis was associated with PPHT (OR = 11.5; 95% CI, 1.58-83.4; = 0.02] and the ET-1 / ET-3 ratio [4.73 (0.9-22.4) vs 1.6 (0.3-10.7 ), P = 0.02] were significantly higher in patients with PPHT than in those without. ET-2 and ET-3 levels did not differ between the two groups. There was no difference in survival between the two groups, although ET- 1 levels were associated with an adverse outcome in Cox regression analysis (HR = 1.11; 95% CI, 1.02-1.22; P = 0.02 per unit increase in ET-1) .CONCLUSION: Our data suggest that ET-1 and the ET- ET-3 ratio are elevated in patients with PPHT and that ET-1 is associated with a poor outcome irrespective of PPHT.