Efficacy of outpatient continuous terlipressin infusions for hepatorenal syndrome
Authors: Abhinav Vasudevan, Zaid Ardalan, Paul Gow, Peter Angus, Adam Testro
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the article by Cavallin et al.1 demonstrating the efficacy of continuous terlipressin infusions in patients with hepatorenal syndrome (HRS). The renal response rates obtained were higher than those reported by Sanyal et al. with bolus administration of terlipressin.2 As highlighted by Cavallin et al., a past pharmacodynamic study of bolus terlipressin demonstrated that its effect on portal pressure lasted less than 4 hours.3 Extrapolating these data over a 24‐hour period, with standard 6‐hourly bolus dosing there may be 8 hours or more where there is no effect of terlipressin on portal pressure or renal perfusion; and this may explain the higher renal response rates observed with continuous infusion of the drug. We have described the novel use of outpatient continuous terlipressin infusion as a bridge to orthotopic liver transplantation (OLT).4 We have now successfully used outpatient infusions in six patients with HRS (Table 1 and Fig. 1). In the past these patients would have remained in hospital. All patients fulfilled the diagnostic criteria for HRS and acute kidney injury as defined by the International Ascites Club.5 Due to concerns over the upward trajectory of the creatinine, patients were commenced on terlipressin before they met the strict definition of HRS type 1. All patients initially received bolus administration of terlipressin (0.85 mg intravenously 6‐hourly) to confirm efficacy and tolerability for a median of 6 days (range 1‐21), following which they were discharged home on a continuous infusion. All patients initially received 3.4 mg of terlipressin per 24‐hour period, with two patients tolerating a dose reduction to 1.7 mg over 24 hours. The reduction in dose was to achieve the lowest infusion dose that maintained renal function. There were no adverse events reported with the infusion. Three patients were bridged to OLT at a median of 21 days (range 1‐37) from commencement of the infusion. Renal function remained stable in the post‐OLT period with a median creatinine at 3 months post‐OLT of 140 μmol/L (range 80‐189) or 1.58 mg/dL (range 0.90‐2.14). One patient reversed the HRS after 27 days of terlipressin and has subsequently remained stable after successful hepatitis C treatment. The remaining two patients had the infusions ceased: one after 4 days due to bleeding from the catheter site and the other after 5 days due to being deemed not suitable for OLT. Transferring care from the hospital to the home resulted in a cost reduction from A$1200 (US$843) to A$281 (US$197) per patient per day. Table 1 - Six Patients Treated With an Outpatient Continuous Terlipressin Infusion Parameter Median (Range) Age (years) 64 (56‐70) Gender Male, n = 6 Etiology of liver disease Alcohol, n = 3 Hepatitis C virus, n = 2 Primary sclerosing cholangitis, n = 1 MELD (at commencement of infusion) 18 (12‐27) Infusion length (days) 13 (1‐50) Creatinine at the commencement of bolus terlipressin Micromoles per liter 225 (175‐306) Milligrams per deciliter 2.55 (1.98‐3.46) Creatinine at the commencement of terlipressin infusion Micromoles per liter 135 (106‐200) Milligrams per deciliter 1.53 (1.20‐2.26) Change in creatinine during infusion Micromoles per liter −14 (−10 to −38) Milligrams per deciliter −0.16 (−0.11 to −0.43) Time to nadir creatinine on terlipressin infusion (days) 8 (1‐36) Abbreviation: MELD, Model for End‐Stage Liver Disease. Figure 1: Creatinine values before, during, and after terlipressin infusion. Abbreviation: Cr, creatinine.Our experience suggests that outpatient continuous terlipressin infusion, when used in the appropriate clinical scenario and under close supervision, is a safe, efficacious, and cost‐effective means of preserving renal function in patients with terlipressin‐dependent HRS who are awaiting OLT.