Prospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2022; 14(2): 429-441
Published online Feb 27, 2022. doi: 10.4254/wjh.v14.i2.429
β-arrestin-2 predicts the clinical response to β-blockers in cirrhotic portal hypertension patients: A prospective study
Sameh A Lashen, Mohammed M Shamseya, Marwa A Madkour, Radwa M Abdel Salam, Sanaa S Mostafa
Sameh A Lashen, Division of Hepatology and Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria 21521, Egypt
Mohammed M Shamseya, Marwa A Madkour, Department of Experimental and Clinical Internal Medicine, Medical Research Institute, Alexandria 21561, Egypt
Radwa M Abdel Salam, Sanaa S Mostafa, Department of Pathology, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt
Author contributions: Lashen SA drafted the manuscript and performed data analysis, participated in study design, was involved with data collection, and performed the endoscopic assessment; Shamseya MM drafted the manuscript, participated in study design, was involved with data collection, and performed the endoscopic assessment; Madkour MA was involved with data collection, drafted the manuscript, performed the Doppler evaluation, and assisted in the data analysis; Abdel Salam RM and Mostafa SS equally drafted the manuscript, were involved with data collection, and performed the pathological analysis; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed approved by the institutional review boards of the Faculty of Medicine, Alexandria University [review number: 0303608]
Clinical trial registration statement: The current study design was not a randomized clinical trial, so registration on the clinical trials database was not done.
Informed consent statement: All study participants provided written consent before study enrollment.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose.
Data sharing statement: There are no additional data available.
CONSORT 2010 statement: All the authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
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: Sameh A Lashen, MD, PhD, Associate Professor, Division of Hepatology and Gastroenterology, Faculty of Medicine, Alexandria University, Champollion Street, El-Khartoum Square, Azarita Medical Campus, Alexandria 21521, Egypt. sameh.lashen@alexmed.edu.eg
Received: November 20, 2021
Peer-review started: November 20, 2021
First decision: December 26, 2021
Revised: January 8, 2022
Accepted: February 15, 2022
Article in press: February 15, 2022
Published online: February 27, 2022
Processing time: 93 Days and 13.8 Hours
Abstract
BACKGROUND

Portal hypertension, a common complication associated with liver cirrhosis, can result in variceal bleeding, which greatly impacts patient survival. Recently, β-arrestin-2 has been shown to predict the acute hemodynamic response to nonselective β-blocker therapy for cirrhotic portal hypertension. However, more data is needed on the long-term effects of and changes in β-arrestin-2 following nonselective β-blocker therapy.

AIM

To investigate the expression and role of β-Arrestin-2 in predicting the long-term response to nonselective β-blockers in cirrhotic portal hypertensive patients.

METHODS

We prospectively enrolled 91 treatment-naïve patients with cirrhotic portal hypertension. Baseline clinical and laboratory data were obtained. Gastroscopy was performed for grading and treating varices and obtaining gastric antral biopsies. We measured the serum and antral expression of β-arrestin-2 and obtained Doppler measurement of the portal vein congestion index. Treatment with nonselective β-blockers was then started. The patients were followed up for 18 mo, after which they have undergone a repeat antral biopsy and re-evaluation of the portal vein congestion index.

RESULTS

A higher serum level and antral expression of β-arrestin-2 was associated with longer bleeding-free intervals, greater reduction in the portal vein congestion index, and improved grade of varices. Among patients with a low β-arrestin-2 expression, 17.6% were nonselective β-blocker responders, whereas, among those with high expression, 95.1% were responders (P < 0.001). A serum β-arrestin-2 value ≥ 2.23 ng/mL was associated with a lower likelihood of variceal bleeding (90% sensitivity and 71% specificity). β-arrestin-2 expression significantly decreased after nonselective β-blocker therapy.

CONCLUSION

β-arrestin-2 expression in cirrhotic portal hypertension predicts the clinical response to long-term nonselective β-blocker treatment. Serum β-arrestin-2 is a potential noninvasive biomarker for selecting the candidate patients for nonselective β-blockers.

Keywords: β-arrestin-2; Portal hypertension; Variceal bleeding; Nonselective beta-blockers; Portal congestion index; Variceal ligation

Core Tip: Gastric antral β-Arrestin-2 (β-Arr-2) expression correlates to portal hypertension in terms of esophageal varices and portal gastropathy. A stronger β-Arr-2 expression is associated with a sustained clinical response to nonselective β-blockers (NSBB) with a longer variceal bleeding-free interval. Patients who experienced variceal bleeding while on NSBB had lower baseline serum and tissue expression of β-Arr-2. In patients with responded to NSBB, the expression of β-Arr-2 was reduced after long-term treatment. The serum level of β-Arr-2 correlates to its antral expression and showed high sensitivity and specificity for defining the subgroup of patients who will respond to NSBB.