Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 12;9(9):CD013103.
doi: 10.1002/14651858.CD013103.pub2.

Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis

Lawrence Mj Best  1 , Suzanne C Freeman, Alex J Sutton, Nicola J Cooper, Eng-Loon Tng, Mario Csenar, Neil Hawkins, Chavdar S Pavlov, Brian R Davidson, Douglas Thorburn, Maxine Cowlin, Elisabeth Jane Milne, Emmanuel Tsochatzis, Kurinchi Selvan Gurusamy
Affiliations

Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis

Lawrence Mj Best et al. Cochrane Database Syst Rev. .

Abstract

Background: Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore fluid balance, the other potential treatments include systemic vasoconstrictor drugs (such as vasopressin analogues or noradrenaline), renal vasodilator drugs (such as dopamine), transjugular intrahepatic portosystemic shunt (TIPS), and liver support with molecular adsorbent recirculating system (MARS). There is uncertainty over the best treatment regimen for hepatorenal syndrome.

Objectives: To compare the benefits and harms of different treatments for hepatorenal syndrome in people with decompensated liver cirrhosis.

Search methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers until December 2018 to identify randomised clinical trials on hepatorenal syndrome in people with cirrhosis.

Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and hepatorenal syndrome. We excluded randomised clinical trials in which participants had previously undergone liver transplantation.

Data collection and analysis: Two authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of hepatorenal syndrome, liver transplantation, and other decompensation events. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, hazard ratio (HR), and mean difference (MD) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.

Main results: We included a total of 25 trials (1263 participants; 12 interventions) in the review. Twenty-three trials (1185 participants) were included in one or more outcomes. All the trials were at high risk of bias, and all the evidence was of low or very low certainty. The trials included participants with liver cirrhosis of varied aetiologies as well as a mixture of type I hepatorenal syndrome only, type II hepatorenal syndrome only, or people with both type I and type II hepatorenal syndrome. Participant age ranged from 42 to 60 years, and the proportion of females ranged from 5.8% to 61.5% in the trials that reported this information. The follow-up in the trials ranged from one week to six months. Overall, 59% of participants died during this period and about 35% of participants recovered from hepatorenal syndrome. The most common interventions compared were albumin plus terlipressin, albumin plus noradrenaline, and albumin alone.There was no evidence of a difference in mortality (22 trials; 1153 participants) at maximal follow-up between the different interventions. None of the trials reported health-related quality of life. There was no evidence of differences in the proportion of people with serious adverse events (three trials; 428 participants), number of participants with serious adverse events per participant (two trials; 166 participants), proportion of participants with any adverse events (four trials; 402 participants), the proportion of people who underwent liver transplantation at maximal follow-up (four trials; 342 participants), or other features of decompensation at maximal follow-up (one trial; 466 participants). Five trials (293 participants) reported number of any adverse events, and five trials (219 participants) reported treatment costs. Albumin plus noradrenaline had fewer numbers of adverse events per participant (rate ratio 0.51, 95% CrI 0.28 to 0.87). Eighteen trials (1047 participants) reported recovery from hepatorenal syndrome (as per definition of hepatorenal syndrome). In terms of recovery from hepatorenal syndrome, in the direct comparisons, albumin plus midodrine plus octreotide and albumin plus octreotide had lower recovery from hepatorenal syndrome than albumin plus terlipressin (HR 0.04; 95% CrI 0.00 to 0.25 and HR 0.26, 95% CrI 0.07 to 0.80 respectively). There was no evidence of differences between the groups in any of the other direct comparisons. In the network meta-analysis, albumin and albumin plus midodrine plus octreotide had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.

Funding: two trials were funded by pharmaceutical companies; five trials were funded by parties who had no vested interest in the results of the trial; and 18 trials did not report the source of funding.

Authors' conclusions: Based on very low-certainty evidence, there is no evidence of benefit or harm of any of the interventions for hepatorenal syndrome with regards to the following outcomes: all-cause mortality, serious adverse events (proportion), number of serious adverse events per participant, any adverse events (proportion), liver transplantation, or other decompensation events. Low-certainty evidence suggests that albumin plus noradrenaline had fewer 'any adverse events per participant' than albumin plus terlipressin. Low- or very low-certainty evidence also found that albumin plus midodrine plus octreotide and albumin alone had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.Future randomised clinical trials should be adequately powered; employ blinding, avoid post-randomisation dropouts or planned cross-overs (or perform an intention-to-treat analysis); and report clinically important outcomes such as mortality, health-related quality of life, adverse events, and recovery from hepatorenal syndrome. Albumin plus noradrenaline and albumin plus terlipressin appear to be the interventions that should be compared in future trials.

PubMed Disclaimer

Conflict of interest statement

None known for any of the authors.

Figures

1
1
The network plots showing the outcomes for which network meta‐analysis was performed. The size of the node (circle) provides a measure of the number of trials in which the particular Intervention was included as one of the intervention groups. The thickness of the line provides a measure of the number of direct comparisons between two nodes (Interventions). Abbreviations: Pent = Pentoxyfylline The individual figures are available in the online supplement.
2
2
Study flow diagram.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
The forest plots for all‐cause mortality and recovery from hepatorenal syndrome for which fixed‐effect model and random‐effects model showed different results. The more conservative random‐effects model was used for interpretation. Abbreviations: Alb = albumin
 Mid = midodrine
 Nor = noradrenaline
 Oct = Octreotide
 Pen = Pentoxyfylline
 Ter = Terlipressin
6
6
Inconsistency Factor (IF) plot showing that there was no evidence of inconsistency for all‐cause mortality, but there was inconsistency for recovery from hepatorenal syndrome, the two outcomes for which inconsistency could be assessed. All‐cause mortality: direct estimate The X‐axis shows the difference in the direct and indirect effect estimates.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013103

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Alessandria 2007 {published data only}
    1. Alessandria C, Marzano A, Ottobrelli A, Debernardi‐Venon W, Todros L, Torrani M, et al. Noradrenaline vs terlipressin in hepatorenal syndrome: a prospective, randomized study. Journal of Hepatology 2006;44 Suppl 2:S83‐4. - PubMed
    1. Alessandria C, Ottobrelli A, Debernardi‐Venon W, Todros L, Cerenzia MT, Martini S, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. Journal of Hepatology 2007;47(4):499‐505. - PubMed
Arora 2018 {published data only}
    1. Arora V, Maiwall R, Choudhury A, Jain P, Kumar G, Sarin SK. Terlipressin is superior to Noradrenaline in the management of acute kidney injury (AKI) in patients with ACLF. Journal of Hepatology 2017;66(1 Suppl 1):S563. - PubMed
    1. Arora V, Maiwall R, Choudhury A, Jain P, Kumar G, Sarin SK. Terlipressin is superior to noradrenaline in management of acute kidney injury in acute on chronic liver failure. Indian Journal of Gastroenterology 2017;36(1 Supplement 1):S7‐8.
    1. Arora V, Maiwall R, Vijayaraghavan R, Jindal A, Saggere Muralikrishna S, Kumar G, et al. Terlipressin is superior to noradrenaline in the management of acute kidney injury in acute on chronic liver failure. Hepatology 2018 August 3 [Epub ahead of print]. [DOI: 10.1002/hep.30208] - DOI - PubMed
Badawy 2013 {published data only}
    1. Badawy S, Meckawy N, Ahmed A. Norepinephrine versus terlipressin in patients with type 1 hepatorenal syndrome refractory to treatment with octreotide, midodrine, and albumin (a prospective randomized comparative study). Egyptian Journal of Cardiothoracic Anesthesia 2013;7(1):13‐8.
    1. Boyer TD, Sanyal AJ, Wong F, Frederick RT, Lake JR, O'Leary JG, et al. Initial report of a large, randomized, double blind, placebo‐controlled, phase 3 trial of terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome (HRS‐1): the reverse study. Hepatology 2014;60 Suppl 1:S255.
Boyer 2016 {published data only}
    1. Boyer TD, Medicis JJ, Pappas SC, Potenziano J, Jamil K. A randomized, placebo‐controlled, double‐blind study to confirm the reversal of hepatorenal syndrome type 1 with terlipressin: the reverse trial design. Journal of Clinical Trials (open access) 2012;4:39‐49.
    1. Boyer TD, Sanyal AJ, Pappas SC, Wong F, Jamil K. Percentage change in serum creatinine (SCR) is a sensitive indicator of therapeutic response to terlipressin in hepatorenal syndrome type 1 (HRS‐1). Journal of Hepatology 2015;62 Suppl 2:S379‐80.
    1. Boyer TD, Sanyal AJ, Wong F, Frederick RT, Lake JR, O'Leary JG, 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(7):1579‐89. - PubMed
Cavallin 2015 {published data only}
    1. Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P, Salerno F, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: a randomized trial. Hepatology 2015;62(2):567‐74. - PubMed
    1. Cavallin M, Merli M, Fasolato S, Toniutto P, Salerno F, Bernardi M. Terlipressin and albumin vs midodrine plus octreotide and albumin in the treatment of hepatorenal syndrome in patients with cirrhosis: results of a controlled clinical trial by the Italian Association for the Study of the Liver. Hepatology 2011;54 Suppl 1:S1426‐7.
Chelarescu 2003 {published data only}
    1. Chelarescu D, Chelarescu O, Crumpei F, Stratan I. Captopril in low dose associated with octreotide in hepatorenal syndrome: a randomized study. Journal of Hepatology 2003;38:56.
Copaci 2013 {published data only}
    1. Copaci I, Chiriac G, Micu L, Mindrut E. Alternative treatments for hepato‐renal syndrome in patients with cirrhosis. Falk Symposium 191. Liver Diseases in 2013: Advances in Pathogenesis and Treatment; 2013 Oct 4‐5; London (UK). http://www.falk‐foundation‐symposia.org/uploads/tx_tocfpshoperw/FS191_London_Abstracts_03.pdf: Falk Foundation, 2013:87.
    1. Copaci I, Micu L, Chiriac G. Reversal of type 1 hepatorenal syndrome with terlipressin and octreotide. Journal of Hepatology 2016;64 Suppl 2:S660.
Daskalopoulos 1985 {published data only}
    1. Daskalopoulos G, Jordan DR, Reynolds TB. Randomized trial of peritoneovenous shunt in the treatment of hepatorenal syndrome (HRS). Gastroenterology 1985;88(5):1655.
Ghosh 2013 {published data only}
    1. Ghosh S, Choudhary NS, Sharma AK, Singh B, Kumar P, Agarwal R, et al. Noradrenaline vs terlipressin in the treatment of type 2 hepatorenal syndrome: a randomized pilot study. Liver International 2013;33(8):1187‐93. - PubMed
    1. Singh V, Ghosh S, Chawla Y, Singh B, Sharma N, Bhalla A, et al. Noradrenaline versus terlipressin in the treatment of hepatorenal syndrome. Gastroenterology 2011;140(5 Suppl 1):S958.
    1. Singh V, Ghosh S, Chawla Y, Singh B, Sharma N, Bhalla A, et al. Noradrenaline versus terlipressin in the treatment of hepatorenal syndrome. Journal of Gastroenterology and Hepatology 2010;25 Suppl 2:A98.
Goyal 2008 {published data only}
    1. Goyal O, Sehgal N, Puri S, Sidhu SS. Terlipressin versus noradrenalin in hepatorenal syndrome: a prospective, randomised, unblinded study. Journal of Gastroenterology and Hepatology 2008;23 Suppl 5:A76.
Goyal 2016 {published data only}
    1. Goyal O, Sidhu SS, Sehgal N, Puri S. Noradrenaline is as effective as terlipressin in hepatorenal syndrome type 1: a prospective, randomized trial. Journal of the Association of Physicians of India 2016;64(9):30‐5. - PubMed
Indrabi 2013 {published data only}
    1. Indrabi RA, Javid G, Zargar SA, Khan BA, Yattoo GN, Shah SH, et al. Noradrenaline is equally effective as terlipressin in reversal of type 1 hepatorenal syndrome: a randomized prospective study. Journal of Clinical and Experimental Hepatology 2013;3 Suppl 1:S97.
Koch 2016 {published data only}
    1. Koch N, Huber W, Hoellthaler J, Mair S, Phillip V, Schmid RM, et al. Racehorse: a randomized controlled trial on goal‐directed therapy of hepatorenal syndrome. Intensive Care Medicine Experimental 2016;4 Suppl 1:350‐1.
Martin‐Llahi 2008 {published data only}
    1. Martin‐Llahi M, Pepin M, Guevara M, Diaz F, Torre A, Monescillo A, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008;134(5):1352‐9. - PubMed
    1. Martin‐Llahi M, Pepin MN, Guevara M, Torre A, Monescillo A, Soriano G, et al. Randomized, comparative study of terlipressin and albumin vs albumin alone in patients with cirrhosis and hepatorenal syndrome. Journal of Hepatology 2007;46 Suppl 1:S36. - PubMed
    1. Whittman D, Boyer T, Sanyal A. Terlipressin and albumin significantly improved renal function in patients with type I hepatorenal syndrome (HRS) enrolled in a randomized, double‐blind, placebo controlled trial. Journal of the American Society of Nephrology 2007;18 Suppl 1:818A.
Mitzner 2000 {published data only}
    1. Mitzner SR, Stange J, Klammt S, Risler T, Erley CM, Bader BD, et al. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transplantation 2000;6(3):277‐86. - PubMed
Neri 2008 {published data only}
    1. Neri S, Pulvirenti D, Malaguarnera M, Cosimo BM, Bertino G, Ignaccolo L. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Digestive Diseases and Sciences 2008;53(3):830‐5. - PubMed
    1. Pulvirenti D, Tsami A. Low doses of terlipressin and albumin in type I hepatorenal syndrome. Italian Journal of Medicine 2008;2:34‐8.
Saif 2018 {published data only}
    1. Saif RU, Dar HA, Sofi SM, Andrabi MS, Javid G, Zargar SA. Noradrenaline versus terlipressin in the management of type 1 hepatorenal syndrome: a randomized controlled study. Indian Journal of Gastroenterology 2018;37(5):424‐9. - PubMed
Sanyal 2008 {published data only}
    1. Boyer TD, Rossaro L, Regenstein F, Teuber P, Garcia‐Tsao G, Sanyal A. Liver transplant affects survival outcomes in patients (pts) with type 1 hepatorenal syndrome (HRS) treated with terlipressin vs placebo. American Journal of Transplantation 2009;9:450.
    1. Boyer TD, Sanyal AJ, Garcia‐Tsao G, Blei A, Carl D, Bexon AS, et al. Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. Journal of Hepatology 2011;55(2):315‐21. - PMC - PubMed
    1. Boyer TD, Sanyal AJ, Garcia‐Tsao G, Regenstein F, Rossaro L, Appenrodt B, et al. Impact of liver transplantation on the survival of patients treated for hepatorenal syndrome type 1. Liver Transplantation 2011;17(11):1328‐32. - PMC - PubMed
    1. Sanyal A, Boyer T, Garcia‐Tsao G, Regenstein F, Rossaro L, Teuber P, et al. A prospective, randomized, double blind, placebo‐controlled trial of terlipressin for type 1 hepatorenal syndrome (HRS). Hepatology 2006;44 Suppl 1:694A. - PMC - PubMed
    1. Sanyal AJ, Boyer T, Garcia‐Tsao G, Regenstein F, Rossaro L, Appenrodt B, et al. A randomized, prospective, double‐blind, placebo‐controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 2008;134(5):1360‐8. - PMC - PubMed
Sharma 2008 {published data only}
    1. Sharma P, Kumar A, Sharma 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. American Journal of Gastroenterology 2008;103(7):1689‐97. - PubMed
    1. Sharma P, Kumar A, Sharma BC, Sarin SK. Nor adrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome: a randomized controlled trial. Hepatology 2006;44 Suppl 1:449A.
Singh 2012 {published data only}
    1. Singh V, Ghosh S, Singh B, Kumar P, Sharma N, Bhalla A, et al. Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study. Journal of Hepatology 2012;56(6):1293‐8. - PubMed
Solanki 2003 {published data only}
    1. 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. Journal of Gastroenterology & Hepatology 2003;18(2):152‐6. - PubMed
Stine 2018 {published data only}
    1. Stine JG, Wang J, Cornella SL, Behm B, Henry Z, Shah NL, et al. Treatment of type‐1 hepatorenal syndrome with pentoxifylline: a randomized placebo controlled, blinded pilot clinical trial. Hepatology 2017;66 Suppl 1:958a. - PMC - PubMed
    1. Stine JG, Wang J, Cornella SL, Behm BW, Henry Z, Shah NL, et al. Treatment of type‐1 hepatorenal syndrome with pentoxifylline: a randomized placebo controlled clinical trial. Annals of Hepatology 2018;17(2):300‐6. - PMC - PubMed
Tavakkoli 2012 {published data only}
    1. Tavakkoli H, Yazdanpanah K, Mansourian M. Noradrenalin versus the combination of midodrine and octreotide in patients with hepatorenal syndrome: randomized clinical trial. International Journal of Preventive Medicine 2012;3(11):764‐9. - PMC - PubMed
Yang 2001 {published data only}
    1. Yang YZ, Dan ZL, Lin NZ, Lin M, Liang KH. Efficacy of terlipressin in treatment of liver cirrhosis with hepatorenal syndrome. Journal of Internal Intensive Medicine 2001;7(3):123‐5.
Zafar 2012 {published data only}
    1. Zafar S, Haque I, Tayyab GU, Khan G, Chaudry N. Role of terlipressin and albumin combination versus albumin alone in hepatorenal syndrome. American Journal of Gastroenterology 2012;107 Suppl 1:S175‐6.

References to studies excluded from this review

Abutaleb 2007 {published data only}
    1. Abutaleb N. Possible increased risk of pulmonary edema in patients with hepatorenal syndrome on adding octreotide to albumin/noradrenaline therapies. Saudi Journal of Kidney Diseases & Transplantation 2007;18(2):261. - PubMed
Ackerman 2002 {published data only}
    1. Ackerman Z, Cominelli F, Reynolds TB. Effect of misoprostol on lbuprofen‐induced renal dysfunction in patients with decompensated cirrhosis: results of a double‐blind placebo‐controlled parallel group study. American Journal of Gastroenterology 2002;97(8):2033‐9. - PubMed
Angeli 1999 {published data only}
    1. Angeli P, Volpin R, Gerunda G, Craighero R, Roner P, Merenda R, et al. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology 1999;29(6):1690‐7. - PubMed
Angeli 2015 {published data only}
    1. Angeli P, Piano S. Is type 2 hepatorenal syndrome still a potential indication for treatment with terlipressin and albumin?. Liver Transplantation 2015;21(11):1335‐7. - PubMed
Antoniades 2003 {published data only}
    1. Antoniades C, Auzinger G. Terlipressin and albumin for the hepatorenal syndrome. Hepatology 2003;37(4):946. - PubMed
Casado Caballero 1996 {published data only}
    1. Casado Caballero FJ, Gallego Rojo FJ, Gonzalez Sanchez M, Rodriguez Tellez M, Guilarte Lopez‐Manas J, Carmona Soria I. Reversal of hepatorenal syndrome with oral misoprostol. Is the dose the key to the response? [Reversion de un sindrome hepatorrenal con misoprostol oral]. Gastroenterologia y Hepatologia 1996;19(3):184‐5. - PubMed
Clewell 1994 {published data only}
    1. Clewell JD, Walker‐Renard P. Prostaglandins for the treatment of hepatorenal syndrome. Annals of Pharmacotherapy 1994;28(1):54‐5. - PubMed
Conn 2000 {published data only}
    1. Conn HO. Prolonged infusion of ornithine plus dopamine in the treatment of the hepatorenal syndrome: a breakthrough?. American Journal of Gastroenterology 2000;95(12):3645‐6. - PubMed
Duhamel 2000 {published data only}
    1. Duhamel C, Mauillon J, Berkelmans I, Bourienne A, Tranvouez JL. Hepatorenal syndrome in cirrhotic patients: terlipressine is a safe and efficient treatment; propranolol and digitalic treatments: precipitating and preventing factors?. American Journal of Gastroenterology 2000;95(10):2984‐5. - PubMed
Durkin 1995 {published data only}
    1. Durkin RJ, Winter SM. Reversal of hepatorenal syndrome with the combination of norepinephrine and dopamine. Critical Care Medicine 1995; Vol. 23, issue 1:202‐4. - PubMed
Elia 2015 {published data only}
    1. Elia C, Sola Verges E, Rodriguez E, Gines P. Transient increase in urine protein excretion during treatment with terlipressin and albumin for type‐1 hepatorenal syndrome. Journal of Hepatology 2015;62(2):493‐5. - PubMed
Gines 2005 {published data only}
    1. Gines P, Terra C, Torre A, Guevara M. Role of albumin in the treatment of hepatorenal syndrome in cirrhosis [Papel de la albumina en el tratamiento del sindrome hepatorrenal en la cirrosis]. Gastroenterologia y Hepatologia 2005;28(2):80‐4. - PubMed
Giostra 1995 {published data only}
    1. Giostra E, Ruedin P, Cunningham M, Mentha G, Favre H, Jolliet P, et al. Sustained effects of ornipressin in hepatorenal syndrome. Journal of Hepatology 1995;22(1):120‐1. - PubMed
Hadengue 1998 {published data only}
    1. Hadengue A, Gadano A, Giostra E, Negro F, Moreau R, Valla D, et al. Terlipressin in the treatment of hepatorenal syndrome (HRS): a double blind cross‐over study. Hepatology 1995;22(4 Suppl 1):165a.
    1. Hadengue A, Gadano A, Moreau R, Giostra E, Durand F, Valla D, et al. Beneficial effects of the 2‐day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome. Journal of Hepatology 1998;29(4):565‐70. - PubMed
Kaffy 1999 {published data only}
    1. Kaffy F, Borderie C, Chagneau C, Ripault MP, Larzilliere I, Silvain C, et al. Octreotide in the treatment of the hepatorenal syndrome in cirrhotic patients. Journal of Hepatology 1999;30(1):174. - PubMed
Kalambokis 2005 {published data only}
    1. Kalambokis G, Milionis H, Elisaf M, Tsianos EV. Terlipressin avoids hemodialysis in the treatment of refractory hyperkalemia associated with renal dysfunction in cirrhosis. American Journal of Medicine 2005;118(9):1051‐2. - PubMed
Kalambokis 2017 {published data only}
    1. Kalambokis GN, Baltayiannis G, Christodoulou D, Christou L. Terlipressin is superior to midodrine/octreotide for hepatorenal syndrome type 1. European Journal of Gastroenterology & Hepatology 2017;29(12):1428‐9. - PubMed
Mullen 2002 {published data only}
    1. Mullen KD. Treatment of hepatorenal syndrome: lessons from the MARS trial. Hepatology 2002;35(2):492‐3. - PubMed
Ortega 2002 {published data only}
    1. Ortega R, Ginès P, Uriz J, Calahorra B, Cárdenas A, las Heras D, et al. Effects of administration of terlipressin with or without albumin in hepatorenal syndrome. Phase II study [Efectos de la administración de terlipresina con o sin albúmina en el síndrome hepatorrenal (SHR). Estudio en fase II]. Gastroenterologia y Hepatologia 2002;25 (Suppl 1):61‐2.
Pauwels 2008 {published data only}
    1. Pauwels A. Effectiveness of terlipressin in hepatorenal syndrome is confirmed [L’efficacité de la terlipressine dans le syndrome hépatorénal est confirmée]. Hépato‐Gastro & Oncologie Digestive 2008;15(6):482‐3.
Pomier‐Layrargues 2003 {published data only}
    1. Pomier‐Layrargues G, Paquin S, Tran A, Hassoun Z. Octreotide in hepatorenal syndrome: a randomized placebo‐controlled cross‐over study. Hepatology 2001;34(4 Suppl 2):544A. - PubMed
    1. 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(1):238‐43. - PubMed
Robertson 2014 {published data only}
    1. Robertson M, Majumdar A, Garrett K, Rumler G, Gow P, Testro A. Continuous outpatient terlipressin infusion for hepatorenal syndrome as a bridge to successful liver transplantation. Hepatology 2014;60(6):2125‐6. - PubMed
Srivastava 2015 {published data only}
    1. Srivastava S, Shalimar, Vishnubhatla S, Prakash S, Sharma H, Thakur B, et al. Randomized controlled trial comparing the efficacy of terlipressin and albumin with a combination of concurrent dopamine, furosemide, and albumin in hepatorenal syndrome. Journal of Clinical & Experimental Hepatology 2015;5(4):276‐85. - PMC - PubMed
Sugerman 1970 {published data only}
    1. Sugerman HJ, Berkowitz HD, Davidson DT, Miller LD. Treatment of the hepatorenal syndrome with metaraminol. Surgical Forum 1970;21:359‐61. - PubMed
Sugerman 1971 {published data only}
    1. Sugerman HJ, Berkowitz HD, Miller LD, Schapiro RH, Fischer J. Metaraminol in "hepatorenal syndrome". New England Journal of Medicine 1971;285(3):180‐1. - PubMed
Testro 2009 {published data only}
    1. Testro AG, Angus PW. Targeting circulatory dysfunction in cirrhosis: terlipressin and the hepatorenal syndrome. Journal of Gastroenterology & Hepatology 2009;24(11):1707‐9. - PubMed
Valer‐Fandó 2004 {published data only}
    1. Valer‐Fandó MP, Serradilla R, González‐García M, González‐Alonso R, Milicua JM, Moreira V, et al. Comparative study of treatment with noradrenaline versus terlipressin in patients with hepatorenal syndrome type 1 [Estudio comparative del tratamiento con terlipresina versus noradrenalina en enfermos con síndrome hepatorrenal tipo 1]. Gastroenterología y Hepatología 2004;27 Suppl 1:69.
Varajic 2017 {published data only}
    1. Varajic B, Mann J, Guilkey K, Persaud A, Furmanek SP, Wiemken TL, et al. High versus low mean arterial pressures in hepatorenal syndrome: a randomized controlled trial. American Journal of Respiratory and Critical Care Medicine 2017;195:A5789.

References to ongoing studies

NCT02770716 {published data only}
    1. NCT02770716. A study to confirm efficacy and safety of terlipressin in HRS type 1 [A multi‐center, randomized, placebo controlled, double‐blind study to confirm efficacy and safety of terlipressin in subjects with hepatorenal syndrome type 1 (the CONFIRM Study)]. clinicaltrials.gov/ct2/show/NCT02770716 (first posted 12 May 2016).
NCT03455322 {published data only}
    1. NCT03455322. Norepinephrine infusion versus midodrine & octreotide in patients with hepatorenal syndrome type 1 [Pros & cons of norepinephrine infusion versus midodrine & octreotide in patients with hepatorenal syndrome type 1 in intensive care unit]. clinicaltrials.gov/ct2/show/NCT03455322 (first posted 6 March 2018).

Additional references

Acevedo 2017
    1. Acevedo JG, Cramp ME. Hepatorenal syndrome: update on diagnosis and therapy. World Journal of Hepatology 2017;9(6):293‐9. - PMC - PubMed
Adam 2012
    1. Adam R, Karam V, Delvart V, O'Grady J, Mirza D, Klempnauer J, et al. Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). Journal of Hepatology 2012;57(3):675‐88. - PubMed
Allegretti 2017
    1. Allegretti AS, Israelsen M, Krag A, Jovani M, Goldin AH, Schulman AR, et al. Terlipressin versus placebo or no intervention for people with cirrhosis and hepatorenal syndrome. Cochrane Database of Systematic Reviews 2017, Issue 6. [DOI: 10.1002/14651858.CD005162.pub4] - DOI - PMC - PubMed
Angeli 2015a
    1. Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Journal of Hepatology 2015;62(4):968‐74. - PubMed
Arroyo 1996
    1. Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology 1996;23(1):164‐76. - PubMed
Caironi 2009
    1. Caironi P, Gattinoni L. The clinical use of albumin: the point of view of a specialist in intensive care. Trasfusione del Sangue 2009;7(4):259‐67. - PMC - PubMed
Chaimani 2012
    1. Chaimani A, Salanti G. Using network meta‐analysis to evaluate the existence of small‐study effects in a network of interventions. Research Synthesis Methods 2012;3(2):161‐76. - PubMed
Chaimani 2013
    1. Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta‐analysis in STATA. PLOS ONE 2013;8(10):e76654. - PMC - PubMed
Chan 2013
    1. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza‐Jeric K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Annals of Internal Medicine 2013;158(3):200‐7. - PMC - PubMed
De Franchis 2015
    1. Franchis R, Baveno VIF. Expanding consensus in portal hypertension: report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. Journal of Hepatology 2015;63(3):743‐52. - PubMed
Dias 2010
    1. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta‐analysis. Statistics in Medicine 2010;29(7‐8):932‐44. - PubMed
Dias 2012a
    1. Dias S, Sutton AJ, Welton NJ, Ades AE. NICE DSU technical support document 3: heterogeneity: subgroups, meta‐regression, bias and bias‐adjustment, September 2011 (last updated April 2012). nicedsu.org.uk/wp‐content/uploads/2016/03/TSD3‐Heterogeneity.final‐repor... (accessed 17 July 2018).
Dias 2012b
    1. Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU technical support document 1: introduction to evidence synthesis for decision making, April 2011 (last updated April 2012). nicedsu.org.uk/wp‐content/uploads/2016/03/TSD1‐Introduction.final_.08.05... (accessed 17 July 2018).
Dias 2014
    1. Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. NICE DSU technical support document 4: inconsistency in networks of evidence based on randomised controlled trials, May 2011 (last updated April 2014). nicedsu.org.uk/wp‐content/uploads/2016/03/TSD4‐Inconsistency.final_.15Ap... (accessed 17 July 2018). - PubMed
Dias 2016
    1. Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU technical support document 2: a generalised linear modelling framework for pairwise and network meta‐analysis of randomised controlled trials, August 2011 (last updated September 2016). nicedsu.org.uk/wp‐content/uploads/2017/05/TSD2‐General‐meta‐analysis‐cor... (accessed 17 July 2018).
Dong 2016
    1. Dong T, Aronsohn A, Gautham Reddy K, Te HS. Rifaximin decreases the incidence and severity of acute kidney injury and hepatorenal syndrome in cirrhosis. Digestive Diseases and Sciences 2016;61(12):3621‐6. - PubMed
EASL 2016
    1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: liver transplantation. Journal of Hepatology 2016;64(2):433‐85. - PubMed
EASL 2018
    1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. Journal of Hepatology 2018 Apr 10 [Epub ahead of print]. [DOI: 10.1016/j.jhep.2018.03.024] - DOI - PubMed
EuroQol 2018
    1. EuroQol. EQ‐5D Instruments: about EQ‐5D, 2018. euroqol.org/eq‐5d‐instruments/ (accessed 17 July 2018).
Fleming 2008
    1. Fleming KM, Aithal GP, Solaymani‐Dodaran M, Card TR, West J. Incidence and prevalence of cirrhosis in the United Kingdom, 1992‐2001: a general population‐based study. Journal of Hepatology 2008;49(5):732‐8. - PubMed
Gines 2009
    1. Gines P, Schrier RW. Renal failure in cirrhosis. New England Journal of Medicine 2009;361(13):1279‐90. - PubMed
Gluud 2018
    1. Gluud C, Nikolova D, Klingenberg SL. Cochrane Hepato‐Biliary Group. About Cochrane (Cochrane Review Groups (CRGs)) 2016, Issue 10. Art. No.: LIVER.
Gurusamy 2019
    1. Gurusamy K, Walmsley M, Davidson BR, Frier C, Fuller B, Madden A, et al. Top research priorities in liver and gallbladder disorders in the UK. BMJ Open 2019;9(3):e025045. - PMC - PubMed
Guyatt 2011
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction ‐ GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2012
    1. Higgins JPT, Jackson D, Barrett JK, Lu G, Ades AE, White IR. Consistency and inconsistency in network meta‐analysis: concepts and models for multi‐arm studies. Research Synthesis Methods 2012;3(2):98‐110. - PMC - PubMed
Hinojosa‐Azaola 2014
    1. Hinojosa‐Azaola A, Salas Nolasco OI, Gonzalez Garay AG, Chavez‐Tapia NC, Solis Galicia C. Transjugular intrahepatic portosystemic shunts for hepatorenal syndrome. Cochrane Database of Systematic Reviews 2014, Issue 3. [DOI: 10.1002/14651858.CD011039] - DOI - PubMed
Hutton 2015
    1. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta‐analyses of health care interventions: checklist and explanations. Annals of Internal Medicine 2015;162(11):777‐84. - PubMed
ICH‐GCP 1997
    1. International Conference on Harmonisation Expert Working Group. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice CFR & ICH Guidelines. Vol. 1, Philadelphia (PA): Barnett International/PAREXEL, 1997.
Israelsen 2017
    1. Israelsen M, Krag A, Allegretti AS, Jovani M, Goldin AH, Winter R W, et al. Terlipressin versus other vasoactive drugs for hepatorenal syndrome. Cochrane Database of Systematic Reviews 2017, Issue 9. [DOI: 10.1002/14651858.CD011532.pub2] - DOI - PMC - PubMed
Jackson 2014
    1. Jackson D, Barrett JK, Rice S, White IR, Higgins JP. A design‐by‐treatment interaction model for network meta‐analysis with random inconsistency effects. Statistics in Medicine 2014;33(21):3639‐54. - PMC - PubMed
Kjaergard 2001
    1. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta‐analyses. Annals of Internal Medicine 2001;135(11):982‐9. - PubMed
Lu 2006
    1. Lu G, Ades AE. Assessing evidence inconsistency in mixed treatment comparisons. Journal of the American Statistical Association 2006;101(474):447‐59.
McPherson 2016
    1. McPherson S, Lucey MR, Moriarty KJ. Decompensated alcohol related liver disease: acute management. BMJ 2016;352:i124. - PubMed
Merion 2010
    1. Merion RM. Current status and future of liver transplantation. Seminars in Liver Disease 2010;30(4):411‐21. - PubMed
Mills 2012
    1. Mills EJ, Ioannidis JP, Thorlund K, Schunemann HJ, Puhan MA, Guyatt GH. How to use an article reporting a multiple treatment comparison meta‐analysis. JAMA 2012;308(12):1246‐53. - PubMed
Moher 1998
    1. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta‐analyses?. Lancet 1998;352(9128):609‐13. - PubMed
Mokdad 2014
    1. Mokdad AA, Lopez AD, Shahraz S, Lozano R, Mokdad AH, Stanaway J, et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Medicine 2014;12:145. - PMC - PubMed
Nanda 2018
    1. Nanda A, Reddy R, Safraz H, Salameh H, Singal AK. Pharmacological therapies for hepatorenal syndrome: a systematic review and meta‐analysis. Journal of Clinical Gastroenterology 2018;52(4):360‐7. - PubMed
Nassar Junior 2014
    1. 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(9):e107466. - PMC - PubMed
NCBI 2018
    1. NCBI. Liver cirrhosis. www.ncbi.nlm.nih.gov/mesh/68008103 (accessed 17 July 2018).
Newell 1992
    1. Newell DJ. Intention‐to‐treat analysis: implications for quantitative and qualitative research. International Journal of Epidemiology 1992;21(5):837‐41. - PubMed
OpenBUGS 3.2.3 [Computer program]
    1. Members of OpenBUGS Project Management Group. OpenBUGS. Version 3.2.3. Members of OpenBUGS Project Management Group, 2014.
Optum 2018
    1. Optum. Patient‐reported outcomes | what we do | SF health surveys | SF‐36v2 Health Survey, 2018. campaign.optum.com/optum‐outcomes/what‐we‐do/health‐surveys/sf‐36v2‐heal... (accessed 14 April 2018).
Puhan 2014
    1. Puhan MA, Schünemann HJ, Murad MH, Li T, Brignardello‐Petersen R, Singh JA, et al. A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta‐analysis. BMJ 2014;349:g5630. - PubMed
Ratib 2015
    1. Ratib S, Fleming KM, Crooks CJ, Walker AJ, West J. Causes of death in people with liver cirrhosis in England compared with the general population: a population‐based cohort study. American Journal of Gastroenterology 2015;110(8):1149‐58. - PubMed
Read 1972
    1. Read AE. Clinical physiology of the liver. British Journal of Anaesthesia 1972;44(9):910‐7. - PubMed
Rice 2017
    1. Rice JB, White AG, Galebach P, Korenblat KM, Wagh A, Lovelace B, et al. The burden of hepatorenal syndrome among commercially insured and Medicare patients in the United States. Current Medical Research and Opinion 2017;33(8):1473‐80. - PubMed
Royle 2003
    1. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591‐603. - PubMed
Salanti 2011
    1. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple‐treatment meta‐analysis: an overview and tutorial. Journal of Clinical Epidemiology 2011;64(2):163‐71. - PubMed
Salanti 2012
    1. Salanti G. Indirect and mixed‐treatment comparison, network, or multiple‐treatments meta‐analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Research Synthesis Methods 2012;3(2):80‐97. - PubMed
Savović 2012a
    1. Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized controlled trials: combined analysis of meta‐epidemiological studies. Health Technology Assessment 2012;16(35):1‐82. - PubMed
Savović 2012b
    1. Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomized controlled trials. Annals of Internal Medicine 2012;157(6):429‐38. - PubMed
Savović 2018
    1. Savović J, Turner RM, Mawdsley D, Jones HE, Beynon R, Higgins JPT, et al. Association between risk‐of‐bias assessments and results of randomized trials in Cochrane Reviews: the ROBES meta‐epidemiologic study. American Journal of Epidemiology 2018;187(5):1113‐22. - PMC - PubMed
Scaglione 2015
    1. Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, et al. The epidemiology of cirrhosis in the United States: a population‐based study. Journal of Clinical Gastroenterology 2015;49(8):690‐6. - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408‐12. - PubMed
Schulz 2010
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ (Clinical Research Ed) 2010;340:c332. - PMC - PubMed
Setiawan 2016
    1. Setiawan VW, Stram DO, Porcel J, Lu SC, Marchand L, Noureddin M. Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: the multiethnic cohort. Hepatology 2016;64(6):1969‐77. - PMC - PubMed
Severini 1993
    1. Severini TA. Bayesian interval estimates which are also confidence intervals. Journal of the Royal Statistical Society. Series B (Methodological) 1993;55(2):533‐40.
Stata/SE 15.1 [Computer program]
    1. StataCorp LLC. Stata/SE. Version 15.1. College Station (TX): StataCorp LLC, 2017.
Tsochatzis 2014
    1. Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet 2014;383(9930):1749‐61. - PubMed
Turner 2012
    1. Turner RM, Davey J, Clarke MJ, Thompson SG, Higgins JP. Predicting the extent of heterogeneity in meta‐analysis, using empirical data from the Cochrane Database of Systematic Reviews. International Journal of Epidemiology 2012;41(3):818‐27. - PMC - PubMed
Van Valkenhoef 2012
    1. Valkenhoef G, Lu G, Brock B, Hillege H, Ades AE, Welton NJ. Automating network meta‐analysis. Research Synthesis Methods 2012;3(4):285‐99. - PubMed
Williams 2014
    1. Williams R, Aspinall R, Bellis M, Camps‐Walsh G, Cramp M, Dhawan A, et al. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014;384(9958):1953‐97. - PubMed
Wong 2011
    1. Wong F, Nadim MK, Kellum JA, Salerno F, Bellomo R, Gerbes A, et al. Working party proposal for a revised classification system of renal dysfunction in patients with cirrhosis. Gut 2011;60(5):702‐9. - PubMed
Wood 2008
    1. Wood L, Egger M, Gluud LL, Schulz KF, Juni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta‐epidemiological study. BMJ 2008;336(7644):601‐5. - PMC - PubMed
Yepes‐Nunez 2019
    1. Yepes‐Nunez JJ, Li SA, Guyatt G, Jack SM, Brozek JL, Beyene J, et al. Development of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Summary of Findings (SoF) table for network meta‐analysis. Journal of Clinical Epidemiology 2019 [Epub ahead of print]. - PubMed

References to other published versions of this review

Best 2018
    1. Best LMJ, Freeman S, Sutton AJ, Hawkins N, Tsochatzis E, Gurusamy KS. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta‐analysis. Cochrane Database of Systematic Reviews 2018, Issue 9. [DOI: 10.1002/14651858.CD013103] - DOI - PMC - PubMed

Publication types

Substances