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Impact of long-term continuous terlipressin infusion on the renin-angiotensin-aldosterone system in patients with decompensated cirrhosis

R. Terbah,Rudolf Hoermann,J. Grace,L. Burrell,Sheila K. Patel,Adam Testro,Avik Majumdar,Marie Sinclair

Published 2025 in Frontline Gastroenterology

ABSTRACT

Background and aims Pooling of blood in the splanchnic circulation due to cirrhotic portal hypertension reduces effective circulating blood volume and activates the renin-angiotensin-aldosterone system (RAAS). This study investigates the effects of long-term continuous terlipressin infusion (CTI) on the RAAS in patients with decompensated cirrhosis. Methods 30 participants with cirrhosis and ascites were enrolled in a prospective crossover study comparing 12 weeks of home CTI to observation. Analysis of plasma renin concentration, aldosterone, ACE and ACE2 activity was performed. Results The median age of participants was 62 years (IQR 57–64), median model for end-stage liver disease-Na was 16 (12.3–20.8) and 73% (n=22) were male. Plasma renin decreased by a mean adjusted difference (MAD) of 479.25 mIU/L (95% CI −652.11 to –313.18, p<0.0001), and aldosterone decreased by a MAD of 698.26 pmol/L (95% CI −1009.28 to –396.30, p<0.0001) on CTI compared with observation. Serum ACE2 activity significantly increased by a MAD of 13.71 pmol/mL/min (95% CI 5.88 to 21.92, p=0.001) on CTI compared with observation, and ACE/ACE2 ratio decreased by a MAD of −0.34 (95% CI −0.52 to –0.17, p<0.0002). Conclusion This study demonstrates for the first time a significant attenuation of the classical RAAS and increase in ACE2 activity in patients with decompensated cirrhosis treated with long-term CTI, confirming the physiological mechanism of action of terlipressin in improving ascites and renal function in these patients. Further studies are required to explore the effect of CTI on the alternate RAAS and to determine whether long-term CTI can modulate the clinical progression of decompensated cirrhosis and prevent the development of complications including hepatorenal syndrome. Trial registration number ACTRN12619000891123.

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