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Combination of terlipressin and noradrenaline versus terlipressin in hepatorenal syndrome with early non-response to terlipressin infusion:  A randomized trial

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Abstract

Background

Terlipressin and noradrenaline are effective in the management of hepatorenal syndrome (HRS). There are no reports on the combination of these vasoconstrictors in type-1 HRS.

Aim

To evaluate terlipressin with or without noradrenaline in type-1 HRS not responding to terlipressin at 48 hours.

Methods

Sixty patients were randomized to receive either terlipressin (group A; n = 30) or a combination of terlipressin and noradrenaline infusion (group B; n = 30). In group A, terlipressin infusion was started at 2 mg/day and increased by 1 mg/day (maximum 12 mg/day). In group B, terlipressin was given at a constant dose of 2 mg/day. Noradrenaline infusion was started at 0.5 mg/h at baseline and increased to 3 mg/h in a stepwise manner. The primary outcome was treatment response at 15 days. Secondary outcomes were 30-day survival, cost–benefit analysis and adverse events.

Results

There was no significant difference in the response rate between the groups (50% vs. 76.7%, p = 0.06) and 30-day survival was similar (36.7% vs. 53.3%, p = 0.13). Treatment was more expensive in group A (USD 750 vs. 350, p < 0.001). Adverse events were more frequent in group A (36.7% vs. 13.3%, p < 0.05).

Conclusions

The combination of noradrenaline and terlipressin infusion results in a non-significantly higher rate of HRS resolution with significantly fewer adverse effects in HRS patients who do not respond to terlipressin within 48 hours.

Trial registration.

Clinicaltrials.gov (NCT03822091).

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References

  1. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilatation hypothesis: A proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151–7.

    Article  CAS  PubMed  Google Scholar 

  2. Sanyal AJ, Boyer T, Garcia-Tsao G,  et al. A randomized prospective double blind, placebo controlled study of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134:1360–8.

    Article  CAS  PubMed  Google Scholar 

  3. Martin-Llahi M, Pepin MN, Guevara M,  et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: A randomized study. Gastroenterology. 2008;134:1352–9.

    Article  CAS  PubMed  Google Scholar 

  4. Rodriguez E, Elia C, Sola E,  et al. Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis. J Hepatol. 2014;60:955–61.

    Article  CAS  PubMed  Google Scholar 

  5. Cavallin M, Kamath PS, Merli M,  et al. Terlipressin plus albumin vs. midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology. 2015;62:567–74.

    Article  CAS  PubMed  Google Scholar 

  6. Boyer TD, Sanyal AJ, Wong F,  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;150:1579–89.

    Article  CAS  PubMed  Google Scholar 

  7. Cavallin M, Piano S, Romano A,  et al. Terlipressin given by continuous intravenous infusion vs. intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study. Hepatology. 2016;63:983–92.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Duvoux C, Zanditenas D, Hezode C,  et al. Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: A pilot study. Hepatology. 2002;36:374–80.

    Article  CAS  PubMed  Google Scholar 

  11. Sharma P, Kumar A, Shrama BC, Sarin SK. An open label, pilot, randomized controlled trial of noradrenaline vs. terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103:1689–97.

    Article  CAS  PubMed  Google Scholar 

  12. Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310-8.

    Google Scholar 

  13. Best LM, Freeman SC, Sutton AJ, et al. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: A network meta-analysis. Cochrane Database Syst Rev. 2019;9:CD013103.

  14. Angeli P, Bernardi M, Villanueva C,  et al. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–60.

    Article  Google Scholar 

  15. John S, Thuluvath PJ. Hyponatremia in cirrhosis: Pathophysiology and management. World J Gastroenterol. 2015;21:3197–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bichet D, Szatalowicz V, Chaimovitz C, Schrier RW. Role of vasopressin in abnormal water excretion in cirrhotic patients. Ann Intern Med. 1982;96:413–7.

    Article  CAS  PubMed  Google Scholar 

  17. Pande G, Hatti M, Rai MK,  et al. Response guided slow infusion of albumin, vasoconstrictors and furosemide improves ascites mobilization and survival in acute on chronic liver failure: A proof-of-concept study. J Inflamm Res. 2022;1:5027–39.

    Article  Google Scholar 

  18. 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. J Hepatol. 2015;62:968–74.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160 012, India

    Virendra Singh, Arka De & Akash Singh

  2. Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, 160 012, India

    Akshaya Jayachandran, Shivani Chandel & Navneet Sharma

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  1. Virendra Singh
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  3. Arka De
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  6. Navneet Sharma
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Contributions

Virendra Singh: conceived the study, design of the study protocol, patient enrolment, data collection and manuscript writing; Akshaya Jayachandran: patient enrolment, data collection and manuscript writing; Arka De: patient enrolment, data collection and analysis, manuscript writing; Akash Singh: patient enrolment and data collection; Shivani Chandel: data collection and analysis; Navneet Sharma: data collection. All authors approved the final version of the manuscript.

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Correspondence to Virendra Singh.

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Conflict of interest 

VS, AJ, AD, AS, SC and NS declare no competing interests.

Informed consent in studies with human subjects

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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The authors are solely responsible for the data and the contents of the paper. In no way, the Honorary Editor-in-Chief, Editorial Board Members, the Indian Society of Gastroenterology or the printer/publishers are responsible for the results/findings and content of this article.

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Singh, V., Jayachandran, A., De, A. et al. Combination of terlipressin and noradrenaline versus terlipressin in hepatorenal syndrome with early non-response to terlipressin infusion:  A randomized trial. Indian J Gastroenterol 42, 388–395 (2023). https://doi.org/10.1007/s12664-023-01356-6

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  • DOI: https://doi.org/10.1007/s12664-023-01356-6

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