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

• Published in: Alimentary pharmacology & therapeutics 2022-10, Vol.56 (8), p.1284-1293
• Main Authors: Wong, Florence, Pappas, Stephen Chris, Reddy, K. Rajender, Vargas, Hugo, Curry, Michael P., Sanyal, Arun, Jamil, Khurram
• Format: Article
• Language: English
• Subjects: Acute-On-Chronic Liver Failure - drug therapy; Albumin; Albumins - therapeutic use; ascites; Blood pressure; cirrhosis; Hepatorenal Syndrome - drug therapy; Humans; liver; Liver Cirrhosis - drug therapy; Liver failure; Lypressin - therapeutic use; Mortality; Original; Placebos; portal hypertension; Respiratory failure; Respiratory Insufficiency - chemically induced; Respiratory Insufficiency - drug therapy; Terlipressin - therapeutic use; Terlipressin in Hepatorenal Syndrome Type 1; Vasoconstrictor Agents - adverse effects
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.17195

Summary Background Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute‐on‐chronic liver failure (ACLF). Aim To assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin. Methods 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. Results 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. Conclusion 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. Terlipressin use in hepatorenal syndrome type 1 (HRS1) patients with grade 3 advanced acute‐on‐chronic liver failure (ACLF) is associated with significantly higher incidence of respiratory failure (9.4% ACLF grade 1–2, 30% ACLF grade 3, p = 0.0002), and 90‐day mortality when compared to patients with HRS1 and ACLF grade 1–2. Therefore, terlipressin should be used with caution in HRS1 patients with grade 3 ACLF.