Terlipressin versus Norepinephrine in the Treatment of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis

Abstract

BackgroundHepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS.MethodsWe searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events.ResultsFour studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23), mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17) and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45) between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83).ConclusionsNorepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.

Hepatorenal syndrome in the era of acute kidney injury

“…A randomized‐controlled trial that compared the efficacy and safety of treatment with terlipressin vs noradrenaline for patients with HRS showed that approximately 40% of patients presented response to treatment in both groups and the adverse event profile was also similar . In a recent meta‐analysis, noradrenaline appeared to be as effective and safe as terlipressin for the management of type‐1 HRS and represents a good alternative treatment . However, the number of patients treated with noradrenaline is small to confirm the effectiveness, and a more systematic review and network meta‐analysis showed a low‐quality evidence supporting the use of noradrenaline to reduce mortality and reverse the HRS …”

Management of renal failure in end‐stage liver disease: A critical appraisal

“…Four subsequent small studies, 3 from the same center, compared bolus terlipressin with norepinephrine infusion. A meta‐analysis of these trials showed no difference in HRS reversal or 30‐day mortality . Adverse events, generally cardiac, were less common in the norepinephrine group.…”

Renal Failure in Patients with Liver Cirrhosis: Novel Classifications, Biomarkers, Treatment

“…There were no differences in frequency and profile of side effects [31]. In a recent meta-analysis, these results were confirmed, and noradrenaline seems to be an effective alternative to terlipressin [33]. Noradrenaline is given by continuous infusion at a dose of 0.5-3 mg/h.…”