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Systematic review with meta‐analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1
Author(s) -
Gifford F. J.,
Morling J. R.,
Fallowfield J. A.
Publication year - 2017
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13912
Subject(s) - terlipressin , medicine , hepatorenal syndrome , midodrine , adverse effect , randomized controlled trial , placebo , cirrhosis , gastroenterology , blood pressure , pathology , alternative medicine , orthostatic vital signs
Summary Background Hepatorenal syndrome type 1 ( HRS 1) 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 HRS 1, in the light of recently published randomised controlled trials ( RCT s). Methods MEDLINE (Ovid SP ), EMBASE , PubMed and Cochrane registers were searched for RCT s reporting efficacy and adverse events related to pharmacological treatment of HRS 1. 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 HRS 1 reversal, creatinine improvement, mortality and adverse events. Results Twelve RCT s enrolling 700 HRS1 patients were included. Treatment with terlipressin and albumin led to HRS 1 reversal more frequently than albumin alone or placebo ( RR : 2.54, 95% CI : 1.51–4.26). Noradrenaline was effective in reversing HRS 1, 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 HRS 1 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.