Investigating potential confounding by indication when considering the association between proton pump inhibitor use, infection, hepatic encephalopathy and mortality in hospitalised decompensated cirrhosis: a post-hoc analysis of the ATTIRE trialResearch in context

Bibliographic Details
Title: Investigating potential confounding by indication when considering the association between proton pump inhibitor use, infection, hepatic encephalopathy and mortality in hospitalised decompensated cirrhosis: a post-hoc analysis of the ATTIRE trialResearch in context
Authors: Louise China, Thais Tittanegro, Dominic Crocombe, Ewan Forrest, Yiannis Kallis, Stephen D. Ryder, Gavin Wright, Nick Freemantle, Alastair O'Brien
Source: EClinicalMedicine, Vol 58, Iss , Pp 101924- (2023)
Publisher Information: Elsevier, 2023.
Publication Year: 2023
Collection: LCC:Medicine (General)
Subject Terms: Spontaneous bacterial peritonitis, Variceal bleeding, Bacterial translocation, Medicine (General), R5-920
More Details: Summary: Background: Proton pump inhibitors (PPIs) are commonly prescribed to prevent and treat upper gastrointestinal ulceration and bleeding. Studies have identified increased incidence of spontaneous bacterial peritonitis and hepatic encephalopathy (HE) in cirrhosis patients taking PPIs. However, results are conflicting, and as PPIs are prescribed for variceal bleeding, a major risk factor for infection and HE, it is challenging to discern whether these associations are causal. Methods: In this post-hoc analysis of the ATTIRE trial, we pooled all patient data to investigate the effects of PPI use on clinical outcomes. ATTIRE was a multicentre, open-label, randomised trial of targeted 20% human albumin solution (HAS) daily infusions versus standard care involving 777 adults with decompensated cirrhosis hospitalised with acute complications and albumin 10 times the incidence of variceal bleeding and near double the 28-day mortality compared to non-PPI patients. However, propensity score matching was not possible as there was such a strong selection of patients for PPI use, that we could not find sufficient non-PPI patients to match to. We found no impact of PPI use on plasma markers of bacterial translocation, infection or systemic inflammation. Interpretations: Our real-world data from a completed randomised trial show that PPIs are widely prescribed in the UK and judicious use appears safe in patients hospitalised with decompensated cirrhosis. However, patients prescribed PPIs had fundamentally different phenotypes to those not prescribed PPIs, a form of confounding by indication, which should be strongly considered when interpreting studies and making recommendations about their use. Funding: Wellcome Trust and Department of Health and Social Care.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2589-5370
Relation: http://www.sciencedirect.com/science/article/pii/S2589537023001013; https://doaj.org/toc/2589-5370
DOI: 10.1016/j.eclinm.2023.101924
Access URL: https://doaj.org/article/dc2220861621493d8a1ad11582960c15
Accession Number: edsdoj.2220861621493d8a1ad11582960c15
Database: Directory of Open Access Journals
More Details
ISSN:25895370
DOI:10.1016/j.eclinm.2023.101924
Published in:EClinicalMedicine
Language:English