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

F J Gifford, J R Morling, Jonathan Fallowfield

Research output: Contribution to journalArticlepeer-review

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 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 versus placebo/no treatment, and two active drugs were included. Meta-analysis was performed for HRS1 reversal, creatinine improvement, mortality and adverse events.

Results
12 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 non-blinded. 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 (RR4.32,95%CI:0.75-24.86).

Conclusion
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.

Original languageEnglish
JournalAlimentary Pharmacology and Therapeutics
Early online date4 Jan 2017
DOIs
Publication statusPublished - Mar 2017

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