Retrospective Cohort Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 16, 2022; 10(23): 8097-8106
Published online Aug 16, 2022. doi: 10.12998/wjcc.v10.i23.8097
Nonselective beta-blocker use is associated with increased hepatic encephalopathy-related readmissions in cirrhosis
Mohammad Amin Fallahzadeh, Sumeet K Asrani, Elliot B Tapper, Giovanna Saracino, Robert S Rahimi
Mohammad Amin Fallahzadeh, Department of Internal Medicine, Baylor University Medical Center, Dallas, TX 75246, United States
Sumeet K Asrani, Giovanna Saracino, Robert S Rahimi, Division of Hepatology, Baylor University Medical Center, Dallas, TX 75246, United States
Elliot B Tapper, Division of Hepatology, University of Michigan, Ann Arbor, MI 48109, United States
Author contributions: Fallahazdeh MA, Asrani SK and Rahimi RS designed the research study; Fallahzadeh MA, Asrani SK, Tapper EB, Saracino G and Rahimi RS performed the acquisition, analysis and interpretation of the data; Fallahzadeh MA, Asrani SK and Rahimi RS drafted the manuscript and all authors contributed to revising the manuscript critically; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Reviewer.
Informed consent statement: According to the IRB protocol and policy, all participants of the study provided informed consent indirectly about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at aminfa91@gmail.com. Consent was not obtained but the presented data are anonymized and risk of identification is low. No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohammad Amin Fallahzadeh, MD, Doctor, Department of Internal Medicine, Baylor University Medical Center, 3500 Gaston Ave, Dallas, TX 75246, United States. aminfa91@gmail.com
Received: March 7, 2022
Peer-review started: March 7, 2022
First decision: April 5, 2022
Revised: April 13, 2022
Accepted: July 11, 2022
Article in press: July 11, 2022
Published online: August 16, 2022
ARTICLE HIGHLIGHTS
Research background

Hepatic encephalopathy (HE) is a cirrhosis complication leading to frequent hospitalizations and imposes a significant economic burden on the healthcare system. Nonselective beta-blockers (NSBBs) are the mainstay of pharmacologic treatment for portal hypertension and in the prevention of variceal bleeding in cirrhosis. The role of NSBBs in the development of HE-related complications is not known.

Research motivation

We hypothesized that since NSBBs decrease cardiac output and portal flow, the decreased metabolic filtering process of liver parenchyma may lead to increased HE-related hospitalizations. If there is a signal that NSBB use is associated with HE-related hospitalizations, further multicenter trials are warranted to explore the impact of NSBBs on HE and other portal hypertension complications.

Research objectives

The main objective of this study was to evaluate the impact of NSBB administration on HE-related readmissions in cirrhotic patients.

Research methods

We performed an observational, retrospective, single-center cohort study including 393 patients with cirrhosis admitted to Baylor University Medical Center for liver-related portal hypertension indications between January 2013 and July 2018. Independent predictors of the first HE-related readmissions were identified using Cox proportional hazards analysis. The cumulative incidence of the first HE-related readmissions between patients receiving NSBBs and not receiving NSBBs was examined using Fine-Gray modeling to account for the competing risk of death or liver transplantation.

Research results

In a cohort of patient with mostly Child class C (49.1%) or B (43.8%) cirrhosis, the cumulative incidence of the first HE-related readmissions was significantly higher in patients taking NSBBs compared to patients not receiving NSBBs (71.8% vs 41.8%, P < 0.0001). In multivariate analysis, after adjusting for demographics, markers of liver disease severity, selective beta-blocker, lactulose and rifaximin use, NSBB use [Hazard ratio: 1.74 (95%CI: 1.29-2.34)] was independently associated with the first HE-related readmissions over a median follow-up of 3.8 years. These results warrant further multicenter clinical trials to explore the impact of NSBBs on HE and other portal hypertension complications.

Research conclusions

NSBB use is patients with advanced cirrhosis is independently associated with increased HE-related readmissions, regardless of liver disease severity or biochemical abnormalities. This can be due to the role of NSBB use in decreasing the systemic perfusion pressure that can ultimately lead to a decrease in hepatic perfusion in advanced cirrhosis that will result in an increased blood ammonia level shunting systemically to the brain.

Research perspectives

As this study was a retrospective study, future prospective cohort and randomized clinical trials are warranted to explore the impact of NSBBs on HE and other portal hypertension complications.