Safety and efficacy of outpatient continuous terlipressin infusion for the treatment of portal hypertensive complications in cirrhosis

Abstract

Background/Aim Therapeutic options are limited for patients with hepatorenal syndrome (HRS), diuretic refractory ascites and hepatic hydrothorax who are awaiting liver transplant. We assessed the safety and efficacy of continuous terlipressin infusion (CTI) for treating these conditions in an outpatient setting. Method All patients treated with CTI from May 2013 through March 2018 at our institution were initiated in-hospital on bolus dose terlipressin therapy for 24−72 h prior to commencing CTI for home therapy. Daily home visits for clinical assessment and medication administration were provided. Adverse events, effects of treatment on renal function, model for end-stage liver disease (MELD) score, and paracentesis/thoracentesis requirements were assessed. Results Twenty-three patients were included (HRS = 17; refractory ascites = 4; refractory hepatic hydrothorax = 2). Median (range) duration of outpatient CTI was 50 (1-437) days with a total of 2482 patient days of treatment. Fourteen patients (60.9%) received a liver transplant; of whom 13 (92.9%) were alive at the end of the study period. There were no cardiac or ischemic complications and no serious adverse events reported. In patients with HRS, median serum creatinine significantly decreased from 202.0 μmol/L at baseline to 125.5 μmol/L at day 14 of CTI (P = 0.0003) and remained stable thereafter. Median MELD score decreased from 22.5 to 19.0 at end of CTI (P = 0.008). Median frequency of paracentesis/thoracentesis was 4 per month prior to CTI versus 1.52 during treatment. Conclusion Transplant-eligible and otherwise stable patients can be managed with CTI at home for an extended duration under supervision without adverse consequences.

Safety, Tolerability, Pharmacokinetics, and Efficacy of Terlipressin Delivered by Continuous Intravenous Infusion in Patients with Cirrhosis and Refractory Ascites

“…In regard to the efficacy, the study proved that the administration of terlipressin is capable to induce significant reductions in the number of LVPs and in the volume of ascites removed, confirming previous evidence of a positive effect of the drug on the pathophysiology of ascites [23]. These results are well in keeping with those of Gow et al who showed, in a pilot study, that the continuous IV infusion of terlipressin in outpatients with refractory ascites was associated with a significant reduction in the number of LVP and volume of ascites removed [17,21].…”

“…The initially proposed regimen of terlipressin for hepatorenal syndrome-1 and esophageal varices was intermittent intravenous (IV) bolus doses; however, results from clinical studies indicate high and potentially unacceptable rates of serious adverse events [18][19]. Some evidence suggests that the safety and tolerability of terlipressin may be improved with administration as a continuous IV infusion [17,18,20,21]. This Phase 2a clinical trial evaluated the safety, pharmacokinetics (PK), and preliminary efficacy of terlipressin administered as a continuous low dose IV infusion for treating patients with cirrhosis and refractory ascites.…”

A Comprehensive Systematic Review of the Latest Management Strategies for Hepatorenal Syndrome: A Complicated Syndrome to Tackle

“…HRS-AKI is reversible with effective pharmacotherapy and puts them on the waiting list for transplantation in a lower place despite being quite ill, providing a disadvantage to patients with HRS‐AKI on this MELD scoring system [ 18 ]. In order to maintain priority for HRS-AKI patients with effective pharmacotherapy, more advances are required [ 19 , 40 ]. The inequality between the donor organ's availability and the recipient waiting for transplantation is also increasing [ 38 , 43 ].…”

Portal Hypertension in Malnutrition and Sarcopenia in Decompensated Cirrhosis—Pathogenesis, Implications and Therapeutic Opportunities

“…In a small study involving five patients with cirrhosis and diuretic-refractory ascites from our institution, 4 weeks of terlipressin treatment significantly reduced paracentesis volume from a median of 22.9 L to 11.9 L [ 153 ]. A later study demonstrated that the frequency of large volume paracentesis significantly decreased by 62% in 23 patients who were treated with terlipressin for a median duration of 51 days [ 154 ]. A study by Bajaj et al involving six patients found that terlipressin treatment resulted in a ≥30% reduction in ascites volume drained during paracentesis in all patients, and a ≥50% increase in the interval between large volume paracentesis was reported in four of the six patients [ 155 ].…”

“…There is evidence for the use of continuous terlipressin infusions in the outpatient setting, with our institution reporting our experience of 23 patients receiving ambulatory terlipressin, while on the waitlist for a liver transplant, for the management of hepatorenal syndrome, refractory ascites or hepatic hydrothorax for a combined total of 2844 days. These data showed not only improvements in renal function and ascites but importantly, no major drug-related adverse events [ 154 ]. A larger patient experience of >100 patients and 12,000 patient days confirming these safety data has been reported in abstract form [ 156 ] and represents the potential for this therapy to be continued in the long term.…”