ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Protein Biochemistry for Basic and Applied Sciences
Neurofilament Light Chain Proteins are a sensitive biomarker of neuronal damage in cirrhotic patients with hepatic encephalopathy
Clelia Asero 1,2
Francesca Polito 1
Maria Stella Franzè 2
Antonio Battaglia 2,3
Claudia Ligresti 2,3
Teresa Maltese 1
IRENE CACCIOLA 4,2
M'Hammed Aguennouz 1
Vincenzo Macaione 1
1. Universita degli Studi di Messina Dipartimento di Medicina Clinica e Sperimentale, Messina, Italy
2. Azienda Ospedaliera Universitaria G Martino di Messina, Messina, Italy
3. Universita degli Studi di Palermo, Palermo, Italy
4. University of Messina, Messina, Italy
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Abstract
Background and Aims Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis. Although traditionally considered reversible, growing evidence suggests that HE episodes may lead to persistent neuronal damage. This study aimed to evaluate the potential role of neurofilament light chain proteins (NfL) as biomarkers for detecting neuronal injury associated with HE. Method Between May 1st, 2024, and April 30th, 2025, 133 patients were consecutively enrolled at the Liver Unit of the University Hospital of Messina. Exclusion criteria were neurological disorders and active alcohol use. Serum NfL concentrations were measured using SIMOA technology. The study design included two phases: 1) evaluation of NfL concentration differences across the study population, 2) analysis of correlations between NfL levels and clinical/biochemical parameters routinely used for HE diagnosis [West Haven criteria, ammonia levels, Animal Naming Test (ANT)], as well as anthropometric and nutritional indicators (BMI, handgrip strength, calf circumference). Results The study population (56.4% males; median age 69 years) included 28 non-cirrhotic (21.1%) and 105 cirrhotic patients (78.9%), 34 of them (32.3%) with a diagnosis of HE. Statistical analysis revealed significant differences in NfL levels across the three groups (p=0.001). ROC curve analysis demonstrated good discriminative ability of NfL for HE detection (p=0.001, Area Under the Curve=0.753). Significant correlations were observed between NfL levels and ANT scores (p=0.001), West Haven grade (p=0.05), ammonia levels (p=0.021), low BMI (p=0.009), reduced handgrip strength (p=0.008) and calf circumference <31 cm (p=0.043). Conclusions NfL is a promising biomarker for HE. Its use in clinical practice may improve early detection and stratification of HE severity in cirrhotic patients.
Summary
Keywords
biomarkers5, Hepatic Encephalopathy1, liver cirrhosis3, Neurofilament Light Chain Proteins2, Portal Hypertension6, sarcopenia4
Received
11 November 2025
Accepted
19 February 2026
Copyright
© 2026 Asero, Polito, Franzè, Battaglia, Ligresti, Maltese, CACCIOLA, Aguennouz and Macaione. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: IRENE CACCIOLA
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