A prospective study to compare the efficacy of noradrenaline verses terlipressin in hepatorenal syndrome in patients with advanced cirrhosis

Abstract

Background: Hepatorenal syndrome (HRS) is functional renal failure occurring in advanced stage liver disease associated with poor prognosis. The best treatment is liver transplantation. Terlipressin is effective in treatment of HRS but noradrenaline has been suggested as cheaper and readily available alternative and we aimed to compare the efficacy of noradrenaline and terlipressin in patients with HRS.Methods: 30 patients were allocated to each group and group A received infusion of noradrenaline at dose of 0.5 mg/hr (maximum 3 mg/hr) and group B received terlipressin at dose 1 mg intravenously 6 hourly until reversal of HRS or completion of 7 days of therapy. Intravenous albumin (20 g/day) was given to both groups. Decrease in serum creatinine and increase in daily urine output and mean arterial pressure (MAP) helped us in comparison.Results: Out of 60 cirrhotics screened, 51 were randomised into group A (N=22) or group B (N=29). Baseline characteristics of both groups were similar. In group A, 0% showed complete response while 31.8% showed partial response but majority (68.2%) showed no response. In group B, 89.7% showed complete response and 6.9% showed partial response. Decrease in serum creatinine in both groups (group A- 3.91±1.58 mg/dl to 3.07±1.68 mg/dl; group B- 3.21±1.24 mg/dl to 1.36±0.87 mg/dl). Both groups showed an increase in MAP (group A- 76.93±6.18 mmHg to 89.49±6.93 mmHg; group B- 75.54±5.51 mmHg to 89.92±5.07 mmHg).Conclusions: Noradrenaline was not as effective as terlipressin in treatment of HRS.

Comparative efficacy of terlipressin and norepinephrine for treatment of hepatorenal syndrome-acute kidney injury: A systematic review and meta-analysis

“…A few trials that initially met our inclusion criteria were excluded upon further evaluation. Of note, a recent trial by Nayyar et al met the inclusion criteria for this meta-analysis but was excluded because results fell significantly outside of the normal distribution when plotted on the forest plot matrix [ 13 ]. In addition, the 0% HRS reversal rate in the norepinephrine arm prevented calculation of an effect size unless corrections were used [ 13 ].…”

“…Of note, a recent trial by Nayyar et al met the inclusion criteria for this meta-analysis but was excluded because results fell significantly outside of the normal distribution when plotted on the forest plot matrix [ 13 ]. In addition, the 0% HRS reversal rate in the norepinephrine arm prevented calculation of an effect size unless corrections were used [ 13 ]. Other studies such as Jha et al and Ullah et al evaluating terlipressin and norepinephrine were not included since they did not evaluate HRS reversal as an endpoint [ 20 , 21 ].…”

“…Since these meta-analyses, additional studies on the comparative efficacy of the 2 treatments have been published [9][10][11][12][13][14]. Thus, with the addition of this new evidence, we conducted a meta-analysis to compare the reported efficacy of terlipressin and norepinephrine for the treatment of HRS-1 or HRS-AKI.…”

Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function

“…The categories of treatment response were (1) complete response: HRS reversal with SCr ≤ 1.5 mg/dL while on treatment, by day 14 or discharge, and (2) no response: partial or no HRS reversal with reduction of SCr < 0.3 mg/dL above the lowest value obtained within the 14 days prior to randomization. Comparative efficacy data were sourced from the randomized head-to-head clinical trials [ 31 – 35 ].…”

“…A pooled analysis of four trials including patients with HRS based on International Club of Ascites 2015 (or similar) diagnosis criteria was used to estimate the response rate of terlipressin + albumin vs. norepinephrine + albumin [ 31 , 33 – 35 ]. A brief overview of the trials is presented in Supplementary Materials Table S1.…”