Critical flicker frequency improves after alcohol detoxification and is associated with liver stiffness

doi:10.3748/wjg.v31.i36.107703

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Sep 28, 2025 (publication date) through Feb 26, 2026

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World Journal of Gastroenterology

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1007-9327

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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.

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 22.4 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.

Keywords: Critical flicker frequency; Hepatic encephalopathy; Alcohol-related liver disease; Fibrosis; Cirrhosis; Transient elastography; Liver stiffness

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.