Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

PLoS One. 2014 Sep 9;9(9):e107466. doi: 10.1371/journal.pone.0107466. eCollection 2014.


Background: Hepatorenal 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.

Methods: We 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.

Results: Four 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).

Conclusions: Norepinephrine 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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Hepatorenal Syndrome / drug therapy*
  • Humans
  • Lypressin / adverse effects
  • Lypressin / analogs & derivatives*
  • Lypressin / therapeutic use
  • Middle Aged
  • Norepinephrine / adverse effects
  • Norepinephrine / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Terlipressin
  • Treatment Outcome
  • Vasoconstrictor Agents / adverse effects
  • Vasoconstrictor Agents / therapeutic use*


  • Vasoconstrictor Agents
  • Lypressin
  • Terlipressin
  • Norepinephrine

Grants and funding

The authors have no support or funding to report.