Chronic Administration of Losartan, an Angiotensin II Receptor Antagonist, is not Effective in Reducing Portal Pressure in Patients with Preascitic Cirrhosis

Tripathi, Dhiraj; Therapondos, George; Lui, Hock F.; Johnston, Neil; Webb, David J.; Hayes, Peter C.
February 2004
American Journal of Gastroenterology;Feb2004, Vol. 99 Issue 2, p390
Academic Journal
OBJECTIVES: Plasma angiotensin II (ANG II) concentrations are elevated in cirrhosis and have been implicated as a cause of portal hypertension. We aimed to study both the systemic and portal hemodynamics, and tolerability after chronic administration of losartan, an ANG II receptor antagonist.METHODS: Twelve patients with preascitic cirrhosis were studied: mean age of 53.8± 3.3 yr; average Child-Pugh score of 5.8± 0.3; alcohol etiology (5), hepatitis B/C (1/3), primary biliary cirrhosis (3). No patients were on diuretics or vasoactive medication. Hemodynamic measurements were performed at baseline and 4 weeks after daily administration of 25 mg losartan.RESULTS: There was no significant change in the hepatic venous pressure gradient (15.4± 1.5 to 13.6± 1.6 mmHg,−11.7%,p= NS), despite a significant reduction in the wedge hepatic venous pressure (20.3± 1.8 to 17.3± 1.8 mmHg,−14.8%,p<0.05). Cardiac output, hepatic blood flow, systemic vascular resistance, creatinine clearance, and natriuresis were unaffected. The plasma renin activity increased significantly from 2.7± 0.4 to 5.2± 1.1 ng/ml/h (p<0.05). There was a significant reduction in the mean arterial pressure from 96.9± 3.3 to 89.3± 3.5 mmHg,−7.8± 3.0% (p= 0.02), with 1 patient experiencing symptomatic hypotension.Chronic administration of low-dose losartan does not lead to a significant reduction in the portal pressure gradient. Losartan is unlikely to be useful in the management of patients with early cirrhosis, who are at risk of variceal bleeding.


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