Portopulmonary hypertension and serum endothelin levels in hospitalized patients with cirrhosis

摘要

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.