@article{a632692b620b44a9925fd02a39a001ee,
title = "Terlipressin use and respiratory failure in patients with hepatorenal syndrome type 1 and severe acute-on-chronic liver failure",
abstract = "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.",
keywords = "ascites, cirrhosis, liver, portal hypertension",
author = "Florence Wong and Pappas, {Stephen Chris} and Reddy, {K. Rajender} and Hugo Vargas and Curry, {Michael P.} and Arun Sanyal and Khurram Jamil",
note = "Funding Information: : Florence Wong reports grants and personal fees from Mallinckrodt Pharmaceuticals and Sequana Medical; and personal fees from Ocelot Bio and River 2 Renal. S Chris Pappas reports personal fees from Durect, Exelixis, HepQuant, Mallinckrodt Pharmaceuticals, and Orphan Therapeutics LLC. K Rajender Reddy reports grants from AbbVie, BMS, Conatus, Exact Sciences, Gilead, Grifols, HCC‐TARGET, HCV‐TARGET, Intercept, Merck, NASH‐TARGET, Mallinckrodt Pharmaceuticals; and personal fees from AbbVie, BMS, Dova, Gilead, Merck, Shionogi, Spark Therapeutics. Hugo Vargas reports grants and other from Mallinckrodt Pharmaceuticals. Michael Curry reports personal fees from Mallinckrodt Pharmaceuticals; and grants from Gilead, Mallinckrodt Pharmaceuticals, and Sonic Incytes. Arun Sanyal holds stock options in Durect, Exhalenz, Genfit, Hemoshear, Indalo, Rivus, Sanyal Bio, and Tiziana; has received paid consulting advisor fees from Albireo, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Eli Lilly, Genentech, Genfit, Gilead, Hemoshear, HistoIndex, Inventiva, Janssen Pharmaceuticals, Mallinckrodt Pharmaceuticals, Madrigal, Merck, NGM Bio, Northsea, Novartis, Novo Nordisk, Path AI, Pfizer, Poxel, Prosciento, Regeneron, Roche, Salix, Sanofi, Siemens, Takeda, Terns, and 89 Bio; is a non‐paid consultant for Amra, Biocellvia, Galectin, Fractyl, Immunron, Intercept, and Perspectum; provided consultant advice for AstraZeneca, for which renumeration was paid to Virginia Commonwealth University; was a member of a Data and Safety Monitoring Board for a study funded by Sequana; has received research grants from Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Eli Lilly, Fractyl, Gilead, Inventiva, Madrigal, Mallinckrodt Pharmaceuticals, Merck, Novartis, and Novo Nordisk; has an ongoing research collaboration without direct funding with Echosense‐Sandhill, Owl, Second Genome, and Siemens; received study drug for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) trial of Imm124 for patients with alcoholic hepatitis from Immuron, without funding; and has received royalties from Elsevier and UpToDate. Khurram Jamil is an employee of Mallinckrodt Pharmaceuticals. All authors have approved the final version of the manuscript. There was no writing support provided for this manuscript. Declaration of personal interests Funding Information: This manuscript was funded by Mallinckrodt Pharmaceuticals. Funding Information: The authors would like to thank Shannon Escalante of Mallinckrodt Pharmaceuticals for her assistance with data curation, methodology, software, and the statistical design and analyses presented in this paper. Declaration of personal interests: Florence Wong reports grants and personal fees from Mallinckrodt Pharmaceuticals and Sequana Medical; and personal fees from Ocelot Bio and River 2 Renal. S Chris Pappas reports personal fees from Durect, Exelixis, HepQuant, Mallinckrodt Pharmaceuticals, and Orphan Therapeutics LLC. K Rajender Reddy reports grants from AbbVie, BMS, Conatus, Exact Sciences, Gilead, Grifols, HCC-TARGET, HCV-TARGET, Intercept, Merck, NASH-TARGET, Mallinckrodt Pharmaceuticals; and personal fees from AbbVie, BMS, Dova, Gilead, Merck, Shionogi, Spark Therapeutics. Hugo Vargas reports grants and other from Mallinckrodt Pharmaceuticals. Michael Curry reports personal fees from Mallinckrodt Pharmaceuticals; and grants from Gilead, Mallinckrodt Pharmaceuticals, and Sonic Incytes. Arun Sanyal holds stock options in Durect, Exhalenz, Genfit, Hemoshear, Indalo, Rivus, Sanyal Bio, and Tiziana; has received paid consulting advisor fees from Albireo, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Eli Lilly, Genentech, Genfit, Gilead, Hemoshear, HistoIndex, Inventiva, Janssen Pharmaceuticals, Mallinckrodt Pharmaceuticals, Madrigal, Merck, NGM Bio, Northsea, Novartis, Novo Nordisk, Path AI, Pfizer, Poxel, Prosciento, Regeneron, Roche, Salix, Sanofi, Siemens, Takeda, Terns, and 89 Bio; is a non-paid consultant for Amra, Biocellvia, Galectin, Fractyl, Immunron, Intercept, and Perspectum; provided consultant advice for AstraZeneca, for which renumeration was paid to Virginia Commonwealth University; was a member of a Data and Safety Monitoring Board for a study funded by Sequana; has received research grants from Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Covance, Eli Lilly, Fractyl, Gilead, Inventiva, Madrigal, Mallinckrodt Pharmaceuticals, Merck, Novartis, and Novo Nordisk; has an ongoing research collaboration without direct funding with Echosense-Sandhill, Owl, Second Genome, and Siemens; received study drug for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) trial of Imm124 for patients with alcoholic hepatitis from Immuron, without funding; and has received royalties from Elsevier and UpToDate. Khurram Jamil is an employee of Mallinckrodt Pharmaceuticals. All authors have approved the final version of the manuscript. There was no writing support provided for this manuscript. Publisher Copyright: {\textcopyright} 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.",
year = "2022",
month = oct,
doi = "10.1111/apt.17195",
language = "English (US)",
volume = "56",
pages = "1284--1293",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell",
number = "8",
}