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Neurofilament Light Chain in Cerebrospinal Fluid and Blood Identifies Patients With Minimal and Overt Hepatic

Elise Jonasson1,2,3, Lea L Grønkjær1,2,3, Birgitte G Jacobsen1,2,3

  • 1Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.

Liver International : Official Journal of the International Association for the Study of the Liver
|July 9, 2026
PubMed
Abstract

Insights

Serum neurofilament light chain (NfL) shows promise as a minimally invasive biomarker for minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy (HE) in cirrhosis patients. NfL levels correlate strongly between cerebrospinal fluid and serum, aiding in diagnosis.

Area of Science:

  • Neurology
  • Hepatology
  • Biomarker Discovery

Background:

  • Minimal hepatic encephalopathy (MHE) is an underdiagnosed complication of liver cirrhosis, often preceding overt hepatic encephalopathy (HE).
  • Current diagnostic standards like the Portosystemic Hepatic Encephalopathy Score (PHES) have limitations in accuracy and resource accessibility.
  • Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers for neuroaxonal and astrocyte injury, respectively.

Purpose of the Study:

  • To investigate the role of NfL and GFAP in cerebrospinal fluid (CSF) and serum as biomarkers across the spectrum of hepatic encephalopathy (HE) in cirrhosis patients.
  • To assess the correlation between CSF and serum NfL and GFAP levels.
  • To evaluate the diagnostic performance of NfL and GFAP in distinguishing HE stages from healthy controls.

Main Methods:

  • A cross-sectional study included 35 cirrhosis patients (MHE and overt HE) and 14 healthy controls (HC).
  • MHE was defined by PHES < -4; overt HE was graded using West Haven Criteria.
  • CSF and serum NfL and GFAP concentrations were measured using single-molecule array technology.

Main Results:

  • CSF and serum NfL concentrations increased progressively from HC to unimpaired patients, MHE, and overt HE (p < 0.0001).
  • Strong correlation observed between CSF and serum NfL (rho = 0.888, p < 0.0001), with high diagnostic accuracy (AUROCs 0.877-0.951).
  • GFAP showed moderate CSF-serum correlation (rho = 0.496, p < 0.0004) and lower discriminatory value compared to NfL.

Conclusions:

  • Neuroaxonal injury in HE is detectable via NfL in both CSF and serum.
  • The strong correlation between CSF and serum NfL suggests serum NfL as a potential minimally invasive biomarker for MHE and overt HE.
  • NfL demonstrates significant potential for diagnosing and monitoring HE in liver cirrhosis.
Keywords:
cirrhosisglial fibrillary acidic proteinhepatic encephalopathyneurofilament light chain

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