Use of terlipressin in the treatment of hepatorenal syndrome: Intravenous infusion versus intravenous boluses; An Open Label, Pilot, Randomized Controlled Study
Main Article Content
Pratap Sagar Tiwari
http://orcid.org/0000-0003-4084-5879
Manoj Aryal
http://orcid.org/0009-0002-1323-3615
Shital Bhandary
http://orcid.org/0000-0002-7483-3043
Sudhamshu KC
http://orcid.org/0000-0001-5493-9521
http://orcid.org/0000-0003-4084-5879
Manoj Aryal
http://orcid.org/0009-0002-1323-3615
Shital Bhandary
http://orcid.org/0000-0002-7483-3043
Sudhamshu KC
http://orcid.org/0000-0001-5493-9521
Abstract
Introduction: The purpose of this study was to evaluate the role of terlipressin in the management of hepatorenal syndrome, focusing on the efficacy of its infusion and bolus regimens.
Objectives: To determine the efficacy and safety of terlipressin intravenous infusion and bolus regimens in treating hepatorenal syndrome.
Materials & Methods: The study employed an open-label, randomized controlled trial design. A total of 56 patients with hepatorenal syndrome were randomly assigned to two groups. The infusion regimen of terlipressin was administered to the TERLI-I group, while the bolus regimen was given to the TERLI-B group. The drug response and its adverse effects were analyzed.
Result: Among the 56 patients, 83.9% responded to the treatment. In the TERLI-I group, 71.4% had a complete response, 14.2% had a partial response, and 14.2% were non-responders. In the TERLI-B group, 60.7% had a complete response, 21.4% had a partial response, and 17.8% were non-responders. Overall, the response to treatment (partial plus complete response) was observed in 85.7% of the TERLI-I group and 82.1% of the TERLI-B group. No significant treatment-related adverse events were observed.
Conclusion: Terlipressin remains the standard of care for the management of patients with hepatorenal syndrome. Both administration regimens were equally effective, with no significant adverse effects.
Keywords:
Cirrhosis, Hepatorenal syndrome, Terlipressin
Article Details
How to Cite
TIWARI, Pratap Sagar et al.
Use of terlipressin in the treatment of hepatorenal syndrome: Intravenous infusion versus intravenous boluses; An Open Label, Pilot, Randomized Controlled Study.
Medical Research Archives, [S.l.], v. 13, n. 12, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7147>. Date accessed: 22 jan. 2026.
doi: https://doi.org/10.18103/mra.v13i12.7147.
Keywords
Cirrhosis, Hepatorenal syndrome, Terlipressin
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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10. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat. 2005;4(4):287-291. doi:10.1002/pst.185
11. Kieser M, Wassmer G. On the Use of the Upper Confidence Limit for the Variance from a Pilot Sample for Sample Size Determination. Biometrical J. 1996;38(8):941-949. doi:10.1002/bimj.4710380806
12. Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48(6):2064-2077. doi:10.1002/hep.22605
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14. Salerno F, Cazzaniga M, Merli M, et al. Diagnosis, treatment and survival of patients with hepatorenal syndrome: A survey on daily medical practice. J Hepatol. 2011;55(6):1241-1248. doi:10. 1016/j.jhep.2011.03.012
15. Belcher JM, Parada XV, Simonetto DA, et al. Terlipressin and the Treatment of Hepatorenal Syndrome: How the CONFIRM Trial Moves the Story Forward. American Journal of Kidney Diseases. 2022;79(5):737-745. doi:10.1053/j.ajkd.2021.08.016
16. Papaluca T, Gow P. Terlipressin: Current and emerging indications in chronic liver disease. J Gastroenterol Hepatol. 2018;33(3):591-598. doi:10 .1111/jgh.14009
17. Solà E, Guevara M, Ginès P. Current treatment strategies for hepatorenal syndrome. Clin Liver Dis (Hoboken). 2013;2(3):136-139. doi:10.1002/cld.209
18. Mattos A, Mattos A, Ribeiro R. Terlipressin Versus Noradrenaline In The Treatment Of Hepatorenal Syndrome – Systematic Review With Meta-Analysis And Full Economic Evaluation. Eur J Gastroenterol Hepatol. 2016;28(3):345-351. doi:10 .1016/j.jval.2015.09.522
19. Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004;40(1):55-64. doi:10.1002/hep.20262
20. Dundar HZ. Management of hepatorenal syndrome. World J Nephrol. 2015;4(2):277. doi:10. 5527/wjn.v4.i2.277
21. Neri S, Pulvirenti D, Malaguarnera M, et al. Terlipressin and Albumin in Patients with Cirrhosis and Type I Hepatorenal Syndrome. Dig Dis Sci. 200 8;53(3):830-835. doi:10.1007/s10620-007-9919-9
22. Boyer TD, Sanyal AJ, Wong F, Frederick R, Lake JR, Jamil K. 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): 1579-1589. doi:10.1053/j.gastro.2016.02.026
23. 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(2):152-156. doi:10.1046/j.1440-1746.2003.02934
24. 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). J Hepatol. 2015;62(2). doi:10.1016/S0168-8278 (15)30417-7
25. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460. doi:10.10 16/j.jhep.2018.03.024
26. Sanyal AJ, Boyer TD, Frederick RT, et al. Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies. Aliment Pharmacol Ther. 2017;45(11):1390-1402. doi:10.1111/apt.14052
27. Wong F, Pappas SC, Curry MP, et al. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med. 202 1;384(9):818-828. doi:10.1056/nejmoa2008290
28. Angeli P, Volpin R, Gerunda G, et al. Reversal of Type 1 Hepatorenal Syndrome With the Administration of Midodrine and Octreotide. Hepatology. 1999; 29(6):1690-1697. doi:10.1002/hep.510290629
29. Escorsell À, Bandi JC, Moitinho E, et al. Time profile of the haemodynamic effects of terlipressin in portal hypertension. J Hepatol. 1997;26(3):621-627. doi:10.1016/s0168-8278(97)80428-x
30. Biggins SW, Angeli P, Garcia‐Tsao G, et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048. doi: 10.1002/hep.31884
31. Bui T, Sandar S, Luna G, Beaman J, Sunderland B, Czarniak P. An investigation of reconstituted terlipressin infusion stability for use in hepatorenal syndrome. Scientific Reports. 2020;10(1). doi:10.10 38/s41598-020-78044-4
32. 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(3):983-992. doi:10.1002/hep.28396
33. Gerbes AL, Huber E, Gülberg V. Terlipressin for hepatorenal syndrome: continuous infusion as an alternative to iv bolus administration. Gastroenterology. 2009;137(3):1179. doi:10.1053/j.gastro.2009.03.064
34. Mukhtar A, Salah M, Aboulfetouh F, et al. The use of terlipressin during living donor liver transplantation: Effects on systemic and splanchnic hemodynamics and renal function*. Crit Care Med. 2011;39(6):132 9-1334. doi:10.1097/ccm.0b013e3182120842
35. Ding C, Wu X, Fan X, He C, Li J. Hemodynamic effects of continuous versus bolus infusion of terlipressin for portal hypertension: A randomized comparison. J Gastroenterol Hepatol. 2013;28(7): 1242-1246. doi:10.1111/jgh.12195
36. Guevara M, Terra C, Nazar A, et al. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J Hepatol. 2012;57(4):759-765. doi:10.1016/j.jhep.2012.06.013
37. Thévenot T, Bureau C, Oberti F, et al. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. J Hepatol. 2015;62(4):822-830. doi:10.1016/j. jhep.2014.11.017
38. Fernández J, Angeli P, Trebicka J, et al. Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis. Clinical Gastroenterology and Hepatology. 2020;18(4):963-973.e14. doi:10.1016/j.cgh.2019.07.055
39. Moore K, Jamil K, Verleger K, et al. Real‐world treatment patterns and outcomes using terlipressin in 203 patients with the hepatorenal syndrome. Aliment Pharmacol Ther. 2020;52(2):351-358. doi: 10.1111/apt.15836
2. Ginès A, Escorsell A, Ginès P, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993;105(1):229-236. doi:10.10 16/0016-5085(93)90031-7
3. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodés J. Peripheral arterial vasodilation hypothesis: A proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8(5):1151-1157. doi:10.1002/hep.1840080532
4. Saner FH, Canbay A, Gerken G, Broelsch CE. Pharmacology, clinical efficacy and safety of terlipressin in esophageal varices bleeding, septic shock and hepatorenal syndrome. Expert Rev Gastroenterol Hepatol. 2007;1(2):207-217. doi:10. 1586/17474124.1.2.207
5. Sagi SV, Mittal S, Kasturi KS, Sood GK. Terlipressin therapy for reversal of type 1 hepatorenal syndrome: A meta‐analysis of randomized controlled trials. J Gastroenterol Hepatol. 2010;25(5):880-885. doi:10 .1111/j.1440-1746.2009.06132.x
6. Nadim MK, Kellum JA, Forni L, et al. Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol. 2024;81(1):163-183. doi:10.10 16/j.jhep.2024.03.031
7. Martín–Llahí M, Pépin M, Guevara M, et al. Terlipressin and Albumin vs Albumin in Patients With Cirrhosis and Hepatorenal Syndrome: A Randomized Study. Gastroenterology. 2008;134(5):1352-1359. doi:10.1053/j.gastro.2008.02.024
8. Sanyal AJ, Boyer T, Garcia–Tsao G, et al. A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome. Gastroenterology. 2008;134(5):1360-1368. doi:10.1053/j.gastro.2008.02.014
9. Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015;64(4): 531-537. doi:10.1136/gutjnl-2014-308874
10. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat. 2005;4(4):287-291. doi:10.1002/pst.185
11. Kieser M, Wassmer G. On the Use of the Upper Confidence Limit for the Variance from a Pilot Sample for Sample Size Determination. Biometrical J. 1996;38(8):941-949. doi:10.1002/bimj.4710380806
12. Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48(6):2064-2077. doi:10.1002/hep.22605
13. Montoliu S, Ballesté B, Planas R, et al. Incidence and Prognosis of Different Types of Functional Renal Failure in Cirrhotic Patients With Ascites. Clinical Gastroenterology and Hepatology. 2010;8 (7):616-622. doi:10.1016/j.cgh.2010.03.029
14. Salerno F, Cazzaniga M, Merli M, et al. Diagnosis, treatment and survival of patients with hepatorenal syndrome: A survey on daily medical practice. J Hepatol. 2011;55(6):1241-1248. doi:10. 1016/j.jhep.2011.03.012
15. Belcher JM, Parada XV, Simonetto DA, et al. Terlipressin and the Treatment of Hepatorenal Syndrome: How the CONFIRM Trial Moves the Story Forward. American Journal of Kidney Diseases. 2022;79(5):737-745. doi:10.1053/j.ajkd.2021.08.016
16. Papaluca T, Gow P. Terlipressin: Current and emerging indications in chronic liver disease. J Gastroenterol Hepatol. 2018;33(3):591-598. doi:10 .1111/jgh.14009
17. Solà E, Guevara M, Ginès P. Current treatment strategies for hepatorenal syndrome. Clin Liver Dis (Hoboken). 2013;2(3):136-139. doi:10.1002/cld.209
18. Mattos A, Mattos A, Ribeiro R. Terlipressin Versus Noradrenaline In The Treatment Of Hepatorenal Syndrome – Systematic Review With Meta-Analysis And Full Economic Evaluation. Eur J Gastroenterol Hepatol. 2016;28(3):345-351. doi:10 .1016/j.jval.2015.09.522
19. Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004;40(1):55-64. doi:10.1002/hep.20262
20. Dundar HZ. Management of hepatorenal syndrome. World J Nephrol. 2015;4(2):277. doi:10. 5527/wjn.v4.i2.277
21. Neri S, Pulvirenti D, Malaguarnera M, et al. Terlipressin and Albumin in Patients with Cirrhosis and Type I Hepatorenal Syndrome. Dig Dis Sci. 200 8;53(3):830-835. doi:10.1007/s10620-007-9919-9
22. Boyer TD, Sanyal AJ, Wong F, Frederick R, Lake JR, Jamil K. 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): 1579-1589. doi:10.1053/j.gastro.2016.02.026
23. 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(2):152-156. doi:10.1046/j.1440-1746.2003.02934
24. 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). J Hepatol. 2015;62(2). doi:10.1016/S0168-8278 (15)30417-7
25. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460. doi:10.10 16/j.jhep.2018.03.024
26. Sanyal AJ, Boyer TD, Frederick RT, et al. Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies. Aliment Pharmacol Ther. 2017;45(11):1390-1402. doi:10.1111/apt.14052
27. Wong F, Pappas SC, Curry MP, et al. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med. 202 1;384(9):818-828. doi:10.1056/nejmoa2008290
28. Angeli P, Volpin R, Gerunda G, et al. Reversal of Type 1 Hepatorenal Syndrome With the Administration of Midodrine and Octreotide. Hepatology. 1999; 29(6):1690-1697. doi:10.1002/hep.510290629
29. Escorsell À, Bandi JC, Moitinho E, et al. Time profile of the haemodynamic effects of terlipressin in portal hypertension. J Hepatol. 1997;26(3):621-627. doi:10.1016/s0168-8278(97)80428-x
30. Biggins SW, Angeli P, Garcia‐Tsao G, et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048. doi: 10.1002/hep.31884
31. Bui T, Sandar S, Luna G, Beaman J, Sunderland B, Czarniak P. An investigation of reconstituted terlipressin infusion stability for use in hepatorenal syndrome. Scientific Reports. 2020;10(1). doi:10.10 38/s41598-020-78044-4
32. 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(3):983-992. doi:10.1002/hep.28396
33. Gerbes AL, Huber E, Gülberg V. Terlipressin for hepatorenal syndrome: continuous infusion as an alternative to iv bolus administration. Gastroenterology. 2009;137(3):1179. doi:10.1053/j.gastro.2009.03.064
34. Mukhtar A, Salah M, Aboulfetouh F, et al. The use of terlipressin during living donor liver transplantation: Effects on systemic and splanchnic hemodynamics and renal function*. Crit Care Med. 2011;39(6):132 9-1334. doi:10.1097/ccm.0b013e3182120842
35. Ding C, Wu X, Fan X, He C, Li J. Hemodynamic effects of continuous versus bolus infusion of terlipressin for portal hypertension: A randomized comparison. J Gastroenterol Hepatol. 2013;28(7): 1242-1246. doi:10.1111/jgh.12195
36. Guevara M, Terra C, Nazar A, et al. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J Hepatol. 2012;57(4):759-765. doi:10.1016/j.jhep.2012.06.013
37. Thévenot T, Bureau C, Oberti F, et al. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. J Hepatol. 2015;62(4):822-830. doi:10.1016/j. jhep.2014.11.017
38. Fernández J, Angeli P, Trebicka J, et al. Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis. Clinical Gastroenterology and Hepatology. 2020;18(4):963-973.e14. doi:10.1016/j.cgh.2019.07.055
39. Moore K, Jamil K, Verleger K, et al. Real‐world treatment patterns and outcomes using terlipressin in 203 patients with the hepatorenal syndrome. Aliment Pharmacol Ther. 2020;52(2):351-358. doi: 10.1111/apt.15836