Introduction: Hepatorenal syndrome (HRS) is a functional renal impairment associated with advanced cirrhosis. The best treatment is liver transplantation; however, many patients die before this can be done. Terlipressin improves renal function in HRS, but recent studies have shown similar effects with the cheaper and more readily available norepinephrine. This review included randomized trials comparing noradrenaline to terlipressin for patients with type 1 HRS, as defined by the International Ascites Club.

Objective: To determine the safety and effectiveness of noradrenaline in the management of HRS in terms of 1) reducing mortality, 2) reversal and 3) occurrence of adverse events

Methodology: For this meta-analysis paper, the researchers utilized an electronic search of databases and manual scanning of reference lists were performed. Standardized eligibility assessment was performed independently by three reviewers. Review Manager 5.0.23 was used to calculate odds ratios (OR) with 95% confidence intervals (CIs) as well as I2 values for inter-trial heterogeneity. Standardized eligibility assessment was performed independently by three reviewers.

Results: Thirty-six articles were found after electronic and manual searching. Three were assessed for validity and included in the final analysis. The total number of patients across all trials was 95. Noradrenaline was found not to differ from terlipressin in terms of 15-day survival rate (OR 01.17; 95% CI: 0.51-2.66), reversal of HRS (OR1.07; 95% CI: 0.47-2.44), and a post-hoc analysis on disease-free survival (OR 0.78; 95% CI: 0.34-1.79). Results of sensitivity analysis were consistent with the previous findings (15-day survival: OR=1.21 95% CI = 0.52-2.83; HRS reversal: OR= 1.33, 95% CI = 0.56-3.13; disease-free survival: 1.35, CI =0.56-3.25). Only transient adverse effects were noted with either drugs.

Conclusion: There is inconclusive evidence that noradrenaline and terlipressin are significantly different in the reversal of HRS and reduction of mortality. Larger trials on noradrenaline or a non-inferiority trial may be needed to establish the equivalence of noradrenaline with terlipressin.

1. Salerno, F., Gerbes, A., Gines, P., Wong, F., and V. Arroyo. Diagnosis, Prevention and Treatment of Hepatorenal syndrome in cirrhosis.Gut 2007;56:1310-1318.
2. Gluud, L., Christensen, K., Christensen E., and A. Krag. Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome. Hepatology 2010;51:576- 584
3. Adebayo, D., Morabito, V., Davenport, A., and R. Jalan. Renal dysfunction in cirrhosis is not just a vasomotor nephropathy. Kidney International 2015; 87: 509-515.
4. Gines P, Guevara M, Arroyo V et al. Hepatorenal syndrome. Lancet 2003; 362: 1819–1827.
5. Arroyo, V., Gins, P., Gerbes, A.L., Dudley, F.J. et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology. 1996; 23: 164176
6. Fabrizi, F., Dixit, V., and P. Martin. Meta-analysis: Terlipressin therapy for the hepatorenal syndrome. Aliment. Pharmacol.Ther 2006;24:935-944.
7. Alessandria, C., Ottobrelli, A., Debernardi-Venon, W., Todros, L., Torrani, Cerenzia, M., Martini, S., Balzola F., Morgando, A., Rizetto M., and A. Marzano. Noradrenalin vs. Terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded pilot study. Journal of Hepatology 2007;47:499-505.
8. Duvoux, C., Zanditenas, D., Hezode, C., Chauvat, A., Monin, JL., Roudot-Thoraval, F., Mallat, A., and D. Dhumeaux. Effects of Noradrenaline and Albumin in Patients with Type I Hepatorenal Syndrome: A Pilot Study. Hepatology 2002;36:374-380.
9. Sharma, P., Kumar A., Sharma, B. and S. Sarin. An Open Label, Pilot, Randomized Controlled Trial of Noradrenaline Versus Terlipressin in the Treatment of Type1 Hepatorenal Syndrome and Predictors of Response. American Journal of Gastroenterology 2008;103:1689-1697.
10. Singh, V., Ghosh, S., Singh, B., Kumar, P., Sharma, N., Bhalla, A., Sharma, A.K., Choudhary, N.S., Chawla, Y and C.K. Nain. Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: A randomized study. Journal of Hepatology 2012;56:1293-1298