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.
OBJECTIVES: Terlipressin improves renal function in hepatorenal syndrome (HRS) is a known fact. However the reason for lack of its long-term survival benefits despite improvement in renal function remains unclear. The aim of this study was to analyze the survival benefits of terlipressin in HRS and to address the issue of non-responder state to terlipressin.
MATERIALS AND METHODS: Electronic databases and relevant articles were searched for all types of studies related to HRS and use of terlipressin in HRS. Reduction in all-cause mortality rate was the primary outcome measure. Reduction in mortality rate due to HRS and other causes of death were also analyzed.
RESULTS: With total 377 patients analyzed from eight eligible studies; terlipressin reduced all-cause mortality rate by 15% (Risk Difference: -0.15%, 95% CI:-0.26 to -0.03). Reduction in the mortality rate due to HRS at three months was 9% (Risk Difference:-0.09%, 95% CI:-0.18 to 0.00).
CONCLUSION: Terlipressin has long term survival benefits perhaps at least up to three months but only with HRS as a cause of death not for other causes of death. Benefits and role of antioxidants like N- Acetylcysteine (NAC) in non-responder patients' needs to be studied further. Long-term use of low dose terlipressin (<4 mg/d) plus albumin and addition of antioxidant NAC to this regimen may help in improving both HRS reversal rate and survival rate in non-responders to terlipressin.
BACKGROUND: Hepatorenal syndrome (HRS) is a common complication in patients with cirrhosis or fulminant liver failure. We systematically reviewed the benefits and harms of using terlipressin, a novel vasoconstricting agent in patients with HRS.
METHODS: We searched MEDLINE, SCOPUS, and conference proceedings for relevant trials of terlipressin. Results were summarized using the random-effects model.
RESULTS: Eight trials (320 participants) were included. When compared with placebo, terlipressin-treated patients had higher HRS reversal (odds ratio [OR] 7.47, 95% confidence interval [CI] 3.17-17.59), mean arterial pressure (weighted mean difference [WMD] 11.26 mmHg, 95% CI 1.52-21), and urine output. There was a significant increase in ischemic adverse events with terlipressin when compared to placebo. There was mild-to-moderate heterogeneity in these analyses. There was no significant difference between terlipressin and noradrenaline in HRS reversal (OR 1.23, 95% CI, 0.43-3.54), mean arterial pressure, and urine output. Side-effect profile did not differ between terlipressin and noradrenaline.
CONCLUSION: Terlipressin improves HRS reversal and other surrogate outcome measures compared with placebo, but no significant differences for these outcomes were noted when comparing terlipressin and noradrenaline. Terlipressin is a potential therapeutic option for HRS, but larger trials comparing terlipressin to other widely used vasoconstrictors are warranted.
OBJECTIVE: To evaluate the efficacy, adverse effect and safety of terlipressin in the treatment of hepatorenal syndrome (HRS). METHODS: Correlated randomized controlled clinical trials (RCTs) comparing terlipressin with other therapies in the treatment of HRS were searched in Medline, Embase, Cochrane Library, VIP and National Knowledge Infrastructure (CNKI). Stata 9.0 was used for meta-analysis. RESULTS: 7 RCTs including 305 cases were selected for analysis in accordance with the enrollment criteria. HRS reversal rate of terlipressin was superior to that of placebo (total OR = 6.76, 95% CI = 3.37-13.56, P = 0.000); Myocardial infarction rate (total OR = 1.37, 95% CI = 0.26-7.31, P = 0.715), arrhythmic rate (total OR = 3.25, 95% CI = 0.49-21.31, P = 0.222), suspected intestinal ischemic rate (total OR = 2.14, 95% CI = 0.46-10.02, P = 0.336) and peripheral ischemic rate (total OR = 1.72, 95% CI = 0.34-8.76, P = 0.516) of terlipressin were similar with those of placebo; Mortality rate of terlipressin was a little lower than that of placebo (total OR = 0.55, 95% CI = 0.31-0.98, P = 0.044). HRS reversal rate (total OR = 0.92, 95% CI = 0.32-2.67, P = 0.877), myocardial infarction rate (total OR = 0.92, 95% CI = 0.06-15.34, P = 0.952), arrhythmic rate (total OR = 0.32, 95% CI = 0.03-3.73, P = 0.364), suspected intestinal ischemic rate (total OR = 0.92, 95% CI = 0.06-15.34, P = 0.952), peripheral ischemic rate (total OR = 0.92, 95% CI = 0.06-15.34, P = 0.952) and mortality rate (total OR = 0.80, 95% CI = 0.29-2.24, P = 0.673) of terlipressin were similar to those of noradrenalin. CONCLUSION: Terlipressin and noradrenalin are effective and safe in the treatment of HRS, the relationship between terlipressin and HRS mortality rate should be elucidated with further studies.
