Elshaarawy O, Lan S, Mueller J, Mueller S. Critical flicker frequency improves after alcohol detoxification and is associated with liver stiffness. World J Gastroenterol 2025; 31(36): 107703 [DOI: 10.3748/wjg.v31.i36.107703]
Corresponding Author of This Article
Sebastian Mueller, PhD, Professor, Center for Alcohol Research, University of Heidelberg, In Neuenheimer Feld 350, Heidelberg 69120, Baden-Württemberg, Germany. sebastian.mueller@urz.uni-heidelberg.de
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Sep 28, 2025; 31(36): 107703 Published online Sep 28, 2025. doi: 10.3748/wjg.v31.i36.107703
Critical flicker frequency improves after alcohol detoxification and is associated with liver stiffness
Omar Elshaarawy, Shuai Lan, Johannes Mueller, Sebastian Mueller
Omar Elshaarawy, Shuai Lan, Johannes Mueller, Sebastian Mueller, Center for Alcohol Research, University of Heidelberg, Heidelberg 69120, Baden-Württemberg, Germany
Omar Elshaarawy, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Menoufia 32511, Egypt
Omar Elshaarawy, Department of Gastroenterology, Liverpool University, Liverpool L78XP, United Kingdom
Co-first authors: Omar Elshaarawy and Shuai Lan.
Author contributions: Elshaarawy O and Mueller J contributed to conceptualization; Lan S conducted the experiments; Mueller J performed the data analysis; Mueller S acquired funding and designed the study; Elshaarawy O and Lan S contributed equally as co-first authors. All authors contributed to writing-draft, writing-revision, and approved to submit the final version.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of University of Heidelberg, No. S150-2015.
Informed consent statement: All study participants, or their legal guardians, provided written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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.
Data sharing statement: There is no additional data available.
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: Sebastian Mueller, PhD, Professor, Center for Alcohol Research, University of Heidelberg, In Neuenheimer Feld 350, Heidelberg 69120, Baden-Württemberg, Germany. sebastian.mueller@urz.uni-heidelberg.de
Received: April 7, 2025 Revised: May 18, 2025 Accepted: August 22, 2025 Published online: September 28, 2025 Processing time: 165 Days and 18.3 Hours
Abstract
BACKGROUND
Critical flicker frequency (CFF) is a quantitative tool for assessing hepatic encephalopathy (HE), particularly minimal HE, which is associated with poor prognosis in liver cirrhosis. Alcohol-related liver disease (ALD) is a leading global cause of cirrhosis; however, the effects of alcohol on CFF and its relationship with liver stiffness (LS) remain underexplored.
AIM
To study the impact of alcohol withdrawal on CFF and its correlation with LS in ALD patients.
METHODS
A total of 108 patients were included: 93 heavy drinkers hospitalized for detoxification, 15 with non-ALD etiologies, and 20 healthy controls. CFF was measured using the Hepatonorm analyzer, and LS via transient elastography (FibroScan). Baseline and post-detoxification assessments were conducted in 57 ALD patients.
RESULTS
The cohort had a mean age of 53.7 ± 13.8 years, with 74% male participants. CFF measurements were reliable, with 97.2% of patients showing an interquartile range < 20%. ALD patients exhibited significantly lower CFF compared to controls. Receiver operating characteristic analysis for overt HE (n = 12) yielded an area under the curve of 0.66 (95% confidence interval: 0.49-0.84, P = 0.0142), with an optimal cutoff of 36.5 Hz. CFF significantly improved post-detoxification. Patients with LS > 17 kPa had lower CFF, while those with intermediate LS showed no significant difference.
CONCLUSION
CFF is influenced by HE severity and acute alcohol exposure, showing improvement after detoxification. Its weak correlation with fibrosis stage suggests that CFF serves as a sensitive neurocognitive marker in ALD.
Core Tip: This study demonstrates that critical flicker frequency (CFF), a non-invasive marker of neurocognitive function, significantly improves following alcohol detoxification in patients with alcohol-related liver disease (ALD). CFF was reduced in ALD patients and correlated with liver stiffness, particularly post-detoxification, highlighting its utility in detecting minimal hepatic encephalopathy. These findings underscore CFF’s value in assessing alcohol-related neurotoxicity and monitoring therapeutic response, supporting its integration into routine evaluation of patients with ALD and cirrhosis.
