Ambrisentan for Treatment of Portopulmonary Hypertension

Ambrisentan for Treatment of Portopulmonary Hypertension (PoPH): a Pilot Study

Portopulmonary hypertension denotes pulmonary hypertension complicating portal hypertension and is present in approximately 5% of cirrhotic patients. Treatment options include prostanoids, sildenafil, and the endothelin-receptor antagonists, bosentan and ambrisentan.

This study investigates the safety and efficacy of ambrisentan in portopulmonary hypertension.

Patients with clinically significant PoPH (resting mean pulmonary arterial pressure >25 mm Hg, pulmonary vascular resistance >400 dynes*s*cm-5) will be offered treatment with ambrisentan. Patients will be followed clinically and hemodynamically up to 12 months after start of treatment.

Inclusion Criteria:

• Adult patients with portal hypertension, age >18 years
• Cirrhosis of any etiology; Child-Pugh class A and B
• Noncirrhotic portal hypertension (e.g. chronic portal vein thrombosis)
• Informed consent

Exclusion Criteria:

• Presence of other causes for pulmonary arterial hypertension
• History of pulmonary embolism or myocardial infarction within 6 months before study start
• Child-Pugh class C
• Presence of hepatocellular carcinoma
• Liver transplantation
• HIV infection
• Severe obstructive or restrictive pulmonary disease (predicted FEV1 or VC <65%, respectively)
• Severe dilated cardiomyopathy (EF <50%)
• Latent left-heart insufficiency
• Pregnancy and lactation
• Esophageal variceal hemorrhage within the last 6 months
• Refractory ascites
• Hepatorenal syndrome
• Persistent hepatic encephalopathy > grade 1
• Bilirubin >3.0 mg/dl
• AST and/or ALT >3x ULN
• Creatinine >2.0 mg/dl
• Known hypersensitivity to ambrisentan