Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1

Gifford, F.J.; Morling, J.R.; Fallowfield, J.A.

Abstract

Background

Hepatorenal syndrome type 1 (HRS1) is a functional, rapidly progressive, potentially reversible form of acute kidney injury occurring in patients with cirrhosis. Characterised by intense renal arterial vasoconstriction, it carries a very poor prognosis. There is a significant unmet need for a widely approved, safe and effective pharmacological treatment.

Aim

To re-evaluate efficacy and safety of pharmacological treatments for HRS1, in the light of recently published randomised controlled trials (RCTs).

Methods

MEDLINE (OvidSP), EMBASE, PubMed and Cochrane registers were searched for RCTs reporting efficacy and adverse events related to pharmacological treatment of HRS1. Search terms included: ‘hepatorenal syndrome’, ‘terlipressin’, ‘noradrenaline’, ‘octreotide’, ‘midodrine’, ‘vasopressin’, ‘dopamine’, ‘albumin’ and synonyms. Comparison of vasoactive drugs vs. placebo/no treatment, and two active drugs were included. Meta-analysis was performed for HRS1 reversal, creatinine improvement, mortality and adverse events.

Results

Twelve RCTs enrolling 700 HRS1 patients were included. Treatment with terlipressin and albumin led to HRS1 reversal more frequently than albumin alone or placebo (RR: 2.54, 95% CI: 1.51–4.26). Noradrenaline was effective in reversing HRS1, but trials were small and nonblinded. Overall, there was mortality benefit with terlipressin (RR: 0.79, 95% CI: 0.63–1.01), but sensitivity analysis including only trials with low risk of selection bias weakened this relationship (RR: 0.87, 95% CI: 0.71–1.06). Notably, there was a significant risk of adverse events with terlipressin therapy (RR: 4.32, 95% CI: 0.75–24.86).

Conclusions

Terlipressin treatment is superior to placebo for achieving HRS1 reversal, but mortality benefit is less clear. Terlipressin is associated with significant adverse events, but infusion regimens may be better tolerated. There is continued need for safe and effective treatment options for hepatorenal syndrome.

Citation

Gifford, F., Morling, J., & Fallowfield, J. (in press). Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1. Alimentary Pharmacology and Therapeutics, https://doi.org/10.1111/apt.13912

• Journal Article Type: Article
• Acceptance Date: Dec 2, 2016
• Online Publication Date: Jan 4, 2017
• Deposit Date: Jan 9, 2017
• Publicly Available Date: Jan 9, 2017
• Journal: Alimentary Pharmacology and Therapeutics
• Print ISSN: 0269-2813
• Electronic ISSN: 1365-2036
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/apt.13912
• Keywords: Hepatorenal syndrome, Vasoactive drugs, Terlipressin, Noradrenaline, Systematic review, Meta-analysis.
• Public URL: https://nottingham-repository.worktribe.com/output/841974
• Publisher URL: http://dx.doi.org/10.1111/apt.13912
• Additional Information: This is the peer reviewed version of the following article: Gifford, F. J., Morling, J. R. and Fallowfield, J. A. (2016), Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1. Aliment Pharmacol Ther., which has been published in final form at http://dx.doi.org/10.1111/apt.13912. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Jan 9, 2017