Terlipressin use and respiratory failure in patients with hepatorenal syndrome type 1 and severe acute-on-chronic liver failure.

Abstract

Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute-on-chronic liver failure (ACLF). To assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin. In the CONFIRM study, we randomised 299 patients with HRS1 2:1 to terlipressin or placebo, both with albumin. At enrolment, all patients were assessed for organ failure (OF) using a validated ACLF grading system. Post hoc analyses assessed the effects of terlipressin vs. placebo on the incidence of RF and 90-day mortality. The incidence of RF with terlipressin (n= 200) was 9.4% in patients with grades 1-2 ACLF, and 30% with grade 3 ACLF (p= 0.0002); no such difference was observed in placebo-treated patients (n= 99) (6.2% grades 1-2 vs. 0% grade 3 ACLF, p> 0.05). RF incidence between terlipressin and placebo in patients with grade 3 ACLF was significant (p= 0.01). Baseline predictors of RF with terlipressin were INR (p= 0.011), mean arterial pressure (p= 0.037), and SpO2 (p= 0.014). Prior albumin as a continuous variable was not a predictor of RF. 90-day survival between terlipressin and placebo arms was similar for grades 1-2 ACLF (55.5% and 56.6%, respectively), but lower for grade 3 ACLF (27.55% vs. 50.0%) (p= 0.122), mainly related to RF. Terlipressin should be used with caution in patients with HRS1 and grade 3 ACLF. Patients with hypoxaemia are at increased risk of RF and mortality.