Neurofilament light chain proteins are a sensitive biomarker of neuronal damage in cirrhotic patients with hepatic encephalopathy

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 1 May 2024, and 30 April 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). Conclusion: NfL is a promising biomarker for HE. Its use in clinical practice may improve early detection and stratification of HE severity in cirrhotic patients.