Gastroenterology
Volume 137, Issue 3 , Pages 1180-1181, September 2009

Reply

Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (Ciberehd), Barcelona, Catalunya, Spain

published online 24 July 2009.

Article Outline

 

A large number of studies including several randomized comparative trials have shown that the vasopressin analogue terlipressin, associated with albumin infusion, is effective in the management of the hepatorenal syndrome (HRS). According to a recent meta-analysis, a positive response to therapy, as defined by reduction of the pretreatment high serum creatinine values <1.5 mg/dl (133 μmol/l), is observed in 52% of patients.1 This figure is slightly higher than the response rate observed in the 2 most recent randomized comparative trials, which is 34%–44%.2, 3 The incidence of adverse events is variable among studies, averaging 29%.1

Because pharmacologic therapy of HRS is still in its early days, there are a number of issues that are unknown. An important issue that is currently unknown is the dose of terlipressin with the best safety/efficacy ratio, because no dose-finding studies have been performed. From the published data it appears that doses of terlipressin as low as 1 mg/8–12 hours (2–3 mg/d) may have similar efficacy to doses of 1 mg/4–6 hours (4–6 mg/d). However, comparison between studies is not adequate to address this issue because sample sizes are small and there are differences in patient populations and in the design of the studies. A starting dose of 0.5–1.0 mg/4–6 hours as IV bolus has been recommended in recent guidelines.4 On the other hand, it is also unknown whether the side effects of terlipressin, particularly cardiovascular side effects, are dose dependent. Again, comparison among studies is problematic because the incidence of side effects may vary according to sample size, patient population studied, and retrospective or prospective nature of the studies.

The letter by Gerbes et al raises the interesting issue of whether the administration of terlipressin as continuous IV infusion has similar efficacy and lower rate of side effects compared with intermittent IV bolus administration. The efficacy rate observed in their patient population (42%) is similar to that reported in previous studies using IV bolus administration and the incidence of cardiovascular side effects is low, at only 9% of patients. In this context, it is important to mention the study by Angeli et al5 reported in preliminary form at the 2009 EASL meeting, comparing IV bolus administration of terlipressin with continuous infusion in a prospective design. In this study, which included 37 patients at the time of presentation of data, the efficacy rate was slightly higher in the group of patients treated with continuous terlipressin infusion compared with that in patients treated with iv bolus (74% vs 50%, respectively), with lower incidence of side effects (44% vs 26%, respectively). The final results of this study are awaited before the question raised by Gerbes et al can be answered.

The introduction of an effective pharmacologic therapy has changed dramatically our approach to management of HRS in cirrhosis. There are, however, a great number of questions that remain unanswered. The answer to these questions would require performing large prospective studies, which are difficult to perform because of the complexity of HRS and the severity of patients with this condition. Nevertheless, the opportunity of advancing our understanding of HRS and improving further the efficacy of treatment should not be missed.

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References 

  1. Fabrizi F, Dixit V, Martin P. Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther. 2006;24:935–944
  2. 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;134:1360–1368
  3. Martín-Llahí M, Pépin MN, Guevara M, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008;134:1352–1359
  4. Salerno F, Gerbes A, Ginès P, et al. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310–1318
  5. Angeli P, Fasolato S, Cavallin M, et al. Terlipressin given as continuous intravenous infusion versus terlipressin given as intravenous boluses in the treatment of type 1 hepatorenal syndrome (HRS) in patients with cirrhosis. J Hepatol. 2009;S73(Suppl 1):175A

 Conflicts of interest The authors disclose no conflicts.

PII: S0016-5085(09)01179-2

doi:10.1053/j.gastro.2009.07.023

Refers to article:

  • Terlipressin for Hepatorenal Syndrome: Continuous Infusion as an Alternative to IV Bolus Administration , 24 July 2009

    Alexander L. Gerbes, Elisabeth Huber, Veit Gülberg
    Gastroenterology September 2009 (Vol. 137, Issue 3, Page 1179)

Gastroenterology
Volume 137, Issue 3 , Pages 1180-1181, September 2009

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