Skip to main content
Erschienen in: Journal of General Internal Medicine 1/2018

18.09.2017

Vasoactive Agents for Hepatorenal Syndrome: A Mixed Treatment Comparison Network Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials

verfasst von: Kannan Sridharan, MBBS, MD, DM, Gowri Sivaramakrishnan, MDS

Erschienen in: Journal of General Internal Medicine | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Hepatorenal syndrome (HRS) is a common complication among patients with cirrhosis, primarily attributable to vasodilation of renal vessels. Vasoactive agents are commonly used to treat HRS. The present network meta-analysis compares the vasoactive agents used in HRS.

Methods

We searched electronic databases for appropriate randomized controlled clinical trials in patients with HRS, comparing active interventions with either placebo or standard of care. The primary outcome was complete HRS reversal; secondary outcomes included partial HRS reversal, mortality, adverse events, and cardiovascular adverse events. The data were pooled using a random effects model. We also carried out direct comparisons for the primary outcome with trial sequential analysis.

Results

A total of 16 studies were included in the systematic review. Rates of complete HRS reversal were significantly higher with terlipressin and noradrenaline combined with albumin than with placebo (OR 6.65, 95% CI: 2.08–21.31 and 6.81, 95% CI: 1.87–24.83, respectively). No significant differences were observed in terms of mortality, partial HRS reversal, or adverse events for any of the interventions. However, cardiovascular adverse events were significantly higher with continuous-infusion terlipressin/albumin (OR 7.07, 95% CI: 1.23–40.62), bolus terlipressin/albumin (OR 7.39, 95% CI: 1.89, 28.94), octreotide/midodrine/albumin (OR 9.85, 95% CI: 1.1, 88.1), and noradrenaline/albumin (OR 15.24, 95% CI: 2.1, 112.6) than with albumin alone. Trial sequential analyses revealed adequate evidence to conclude that terlipressin combined with albumin was effective in achieving complete HRS reversal.

Discussion

Terlipressin combined with albumin shows strong evidence of improving short-term survival in patients with type 1 but not type 2 HRS. Through indirect comparison, noradrenaline with albumin was also associated with significant benefits in terms of HRS reversal.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Ginès A, Escorsell A, Ginès P, Saló J, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterol. 1993;105:229-36.CrossRef Ginès A, Escorsell A, Ginès P, Saló J, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterol. 1993;105:229-36.CrossRef
2.
Zurück zum Zitat Ginès P, Martin PY, Niederberger M. Prognostic significance of renal dysfunction in cirrhosis. Kidney Int Suppl. 1997;61:S77-82.PubMed Ginès P, Martin PY, Niederberger M. Prognostic significance of renal dysfunction in cirrhosis. Kidney Int Suppl. 1997;61:S77-82.PubMed
4.
Zurück zum Zitat Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310-8.PubMedPubMedCentral Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310-8.PubMedPubMedCentral
5.
Zurück zum Zitat European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397-417.CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397-417.CrossRef
7.
Zurück zum Zitat Fabrizi F, Dixit V, Martin P. Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther. 2006;24:935-44.CrossRef Fabrizi F, Dixit V, Martin P. Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther. 2006;24:935-44.CrossRef
9.
Zurück zum Zitat ASMKBYDSS A. Prospective randomized controlled trial of concurrent triple therapy for hepatorenal syndrome. J Gastroenterol Hepatol. 2004;19(S7):A119.CrossRef ASMKBYDSS A. Prospective randomized controlled trial of concurrent triple therapy for hepatorenal syndrome. J Gastroenterol Hepatol. 2004;19(S7):A119.CrossRef
10.
Zurück zum Zitat Greco T, Biondi-Zoccai G, Saleh O, et al. The attractiveness of network meta-analysis: a comprehensive systematic and narrative review. Heart Lung Vessel. 2015;7:133-142.PubMedPubMedCentral Greco T, Biondi-Zoccai G, Saleh O, et al. The attractiveness of network meta-analysis: a comprehensive systematic and narrative review. Heart Lung Vessel. 2015;7:133-142.PubMedPubMedCentral
11.
Zurück zum Zitat Hutton B, Salanti G, Caldwell DM, et al. The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations. Ann Intern Med. 2015;162:777-784.CrossRef Hutton B, Salanti G, Caldwell DM, et al. The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations. Ann Intern Med. 2015;162:777-784.CrossRef
12.
13.
Zurück zum Zitat Sedgwick P, Marston L. How to read a funnel plot in a meta-analysis. BMJ. 2015;351:h4718.CrossRef Sedgwick P, Marston L. How to read a funnel plot in a meta-analysis. BMJ. 2015;351:h4718.CrossRef
14.
Zurück zum Zitat Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539-1558.CrossRef Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539-1558.CrossRef
16.
Zurück zum Zitat O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35:549-56.CrossRef O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35:549-56.CrossRef
18.
Zurück zum Zitat Alessandria C, Ottobrelli A, Debernardi-Venon W, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007 ;47:499-505.CrossRef Alessandria C, Ottobrelli A, Debernardi-Venon W, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007 ;47:499-505.CrossRef
19.
Zurück zum Zitat Boyer TD, Sanyal AJ, Wong F, REVERSE study investigators, et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterology. 2016;150:1579-1589.e2.CrossRef Boyer TD, Sanyal AJ, Wong F, REVERSE study investigators, et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterology. 2016;150:1579-1589.e2.CrossRef
20.
Zurück zum Zitat Cavallin M, Kamath PS, Merli M, Italian Association for the study of the liver study group on hepatorenal syndrome, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology. 2015;62:567-74.CrossRef Cavallin M, Kamath PS, Merli M, Italian Association for the study of the liver study group on hepatorenal syndrome, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology. 2015;62:567-74.CrossRef
21.
Zurück zum Zitat Cavallin M, Piano S, Romano A, et al. Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study. Hepatology. 2016;63:983-92.CrossRef Cavallin M, Piano S, Romano A, et al. Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study. Hepatology. 2016;63:983-92.CrossRef
22.
Zurück zum Zitat Ghosh S, Choudhary NS, Sharma AK, et al. Noradrenaline vs terlipressin in the treatment of type 2 hepatorenal syndrome: a randomized pilot study. Liver Int. 2013;33:1187-93.CrossRef Ghosh S, Choudhary NS, Sharma AK, et al. Noradrenaline vs terlipressin in the treatment of type 2 hepatorenal syndrome: a randomized pilot study. Liver Int. 2013;33:1187-93.CrossRef
23.
Zurück zum Zitat Indrabi RA, Javid G, Zargar SA, et al. Noradrenaline is equally effective as terlipressin in reversal of type 1 hepatorenal syndrome: A randomized prospective study. J Clin Exp Hep. 2013;13:S97.CrossRef Indrabi RA, Javid G, Zargar SA, et al. Noradrenaline is equally effective as terlipressin in reversal of type 1 hepatorenal syndrome: A randomized prospective study. J Clin Exp Hep. 2013;13:S97.CrossRef
24.
Zurück zum Zitat Martín-Llahí M, Pépin MN, Guevara M, Díaz F, Torre A, TAHRS Investigators, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterol. 2008;134:1352-9.CrossRef Martín-Llahí M, Pépin MN, Guevara M, Díaz F, Torre A, TAHRS Investigators, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterol. 2008;134:1352-9.CrossRef
25.
Zurück zum Zitat Neri S, Pulvirenti D, Malaguarnera M, et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci. 2008;53:830-5.CrossRef Neri S, Pulvirenti D, Malaguarnera M, et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci. 2008;53:830-5.CrossRef
26.
Zurück zum Zitat Pomier-Layrargues G, Paquin SC, Hassoun Z, Lafortune M, Tran A. Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study. Hepatology. 2003;38:238-43.CrossRef Pomier-Layrargues G, Paquin SC, Hassoun Z, Lafortune M, Tran A. Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study. Hepatology. 2003;38:238-43.CrossRef
27.
Zurück zum Zitat Sanyal AJ, Boyer T, Garcia-Tsao G, Terlipressin Study Group, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterol. 2008;134:1360-8.CrossRef Sanyal AJ, Boyer T, Garcia-Tsao G, Terlipressin Study Group, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterol. 2008;134:1360-8.CrossRef
28.
Zurück zum Zitat Sharma P, Kumar A, Shrama BC, Sarin SK. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103:1689-97.CrossRef Sharma P, Kumar A, Shrama BC, Sarin SK. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103:1689-97.CrossRef
29.
Zurück zum Zitat Singh V, Ghosh S, Singh B, et al. Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study. J Hepatol. 2012;56:1293-8.CrossRef Singh V, Ghosh S, Singh B, et al. Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study. J Hepatol. 2012;56:1293-8.CrossRef
30.
Zurück zum Zitat Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol. 2003;18:152-6.CrossRef Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol. 2003;18:152-6.CrossRef
31.
Zurück zum Zitat Srivastava S, Shalimar, Vishnubhatla S, et al. Randomized controlled trial comparing the efficacy of terlipressin and albumin with a combination of concurrent dopamine, furosemide, and albumin in hepatorenal syndrome. J Clin Exp Hepatol. 2015;5:276-85.CrossRef Srivastava S, Shalimar, Vishnubhatla S, et al. Randomized controlled trial comparing the efficacy of terlipressin and albumin with a combination of concurrent dopamine, furosemide, and albumin in hepatorenal syndrome. J Clin Exp Hepatol. 2015;5:276-85.CrossRef
32.
Zurück zum Zitat Tavakkoli H, Yazdanpanah K, Mansourian M. Noradrenaline versus the combination of midodrine and octreotide in patients with hepatorenal syndrome: randomized clinical trial. Int J Prev Med. 2012;3:764-9.PubMedPubMedCentral Tavakkoli H, Yazdanpanah K, Mansourian M. Noradrenaline versus the combination of midodrine and octreotide in patients with hepatorenal syndrome: randomized clinical trial. Int J Prev Med. 2012;3:764-9.PubMedPubMedCentral
33.
Zurück zum Zitat Zafar S, Haque I, Tayyab GU, Khan G, Chaudry N. Role of terlipressin and albumin combination versus albumin alone in hepatorenal syndrome. Am J Gasteroenterol. 2012;107:S175-S176. Zafar S, Haque I, Tayyab GU, Khan G, Chaudry N. Role of terlipressin and albumin combination versus albumin alone in hepatorenal syndrome. Am J Gasteroenterol. 2012;107:S175-S176.
34.
Zurück zum Zitat Briglia AE, Anania FA. Hepatorenal syndrome. Definition, pathophysiology, and intervention. Crit Care Clin. 2002;18:345-73.CrossRef Briglia AE, Anania FA. Hepatorenal syndrome. Definition, pathophysiology, and intervention. Crit Care Clin. 2002;18:345-73.CrossRef
35.
Zurück zum Zitat Erly B, Carey WD, Kapoor B, McKinney JM, Tam M, Wang W. Hepatorenal syndrome: a review of pathophysiology and current treatment options. Semin Intervent Radiol. 2015;32:445-454.CrossRef Erly B, Carey WD, Kapoor B, McKinney JM, Tam M, Wang W. Hepatorenal syndrome: a review of pathophysiology and current treatment options. Semin Intervent Radiol. 2015;32:445-454.CrossRef
36.
Zurück zum Zitat Wadei HM, Mai ML, Ahsan N, Gonwa TA. Hepatorenal syndrome: pathophysiology and management. Clin J Am Soc Nephrol. 2006;1:1066-79.CrossRef Wadei HM, Mai ML, Ahsan N, Gonwa TA. Hepatorenal syndrome: pathophysiology and management. Clin J Am Soc Nephrol. 2006;1:1066-79.CrossRef
37.
Zurück zum Zitat Kiszka-Kanowitz M, Henriksen JH, Hansen EF, Moller S, Bendtsen F. Effect of terlipressin on blood volume distribution in patients with cirrhosis. Scand J Gastroenterol. 2004;39:486–492.CrossRef Kiszka-Kanowitz M, Henriksen JH, Hansen EF, Moller S, Bendtsen F. Effect of terlipressin on blood volume distribution in patients with cirrhosis. Scand J Gastroenterol. 2004;39:486–492.CrossRef
38.
Zurück zum Zitat Nassar Junior AP, Farias AQ, D’Albuquerque LA, Carrilho FJ, Malbouisson LM. Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis. PLoS One. 2014;9:e107466.CrossRef Nassar Junior AP, Farias AQ, D’Albuquerque LA, Carrilho FJ, Malbouisson LM. Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis. PLoS One. 2014;9:e107466.CrossRef
39.
Zurück zum Zitat Ginès P. Hepatorenal syndrome, pharmacological therapy, and liver transplantation. Liver Transpl. 2011;17:1244-6.CrossRef Ginès P. Hepatorenal syndrome, pharmacological therapy, and liver transplantation. Liver Transpl. 2011;17:1244-6.CrossRef
Metadaten
Titel
Vasoactive Agents for Hepatorenal Syndrome: A Mixed Treatment Comparison Network Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials
verfasst von
Kannan Sridharan, MBBS, MD, DM
Gowri Sivaramakrishnan, MDS
Publikationsdatum
18.09.2017
Verlag
Springer US
Erschienen in
Journal of General Internal Medicine / Ausgabe 1/2018
Print ISSN: 0884-8734
Elektronische ISSN: 1525-1497
DOI
https://doi.org/10.1007/s11606-017-4178-8

Weitere Artikel der Ausgabe 1/2018

Journal of General Internal Medicine 1/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.