Published online Apr 27, 2022. doi: 10.4254/wjh.v14.i4.827
Peer-review started: July 5, 2021
First decision: November 11, 2021
Revised: November 22, 2021
Accepted: March 25, 2022
Article in press: March 25, 2022
Published online: April 27, 2022
Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis, counterbalancing vasoconstriction and anti-natriuretic factors. The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies, and definitive results are lacking.
To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.
We searched MEDLINE, Web of Science, Scopus, Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites. Inclusion was not limited by treatment duration or dose, or by follow-up duration. Both randomised controlled trials and non-randomised studies were eligible for inclusion. The primary outcome was change in renal sodium excretion. Secondary outcomes included safety measures and changes in renal water excretion, plasma aldosterone concentration, and plasma renin activity.
Twenty-two studies were included. Atrial natriuretic peptide (ANP) was the only intensively studied treatment. Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of > 30 ng/kg/min were administered compared with ≤ 30 ng/kg/min (P < 0.01). Moreover, natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites (P < 0.01). ANP infusions increased renal water excretion, although without reaching a statistically significant dose-response gradient. Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders (P < 0.01). Blood pressure decreases occurred less frequently when ANP doses ≤ 30 ng/kg/min were applied. The quality of evidence for a natriuretic response to ANP was low, mainly due to small sample sizes and considerable between-study heterogeneity. Data were sparse for the other natriuretic peptides; B-type natriuretic peptide and urodilatin.
Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites. Continuous infusion rates > 30 ng/kg/min are the most effective. However, safety increases with infusion rates ≤ 30 ng/kg/min.
Core Tip: Pharmacotherapies for cirrhotic ascites have remained largely unchanged for the past four decades. 5%-10% of cirrhosis patients with ascites become refractory to available treatments, and the majority of these patients require frequent large-volume paracenteses. This justifies a continued search for new and improved treatments for ascites. This is the first systematic review and meta-analysis to investigate the effects and safety of natriuretic peptides as treatment of cirrhotic ascites. We demonstrate a significant natriuretic effect of intravenously administered atrial natriuretic peptide and summarise the safety findings.