Neurofilament light chain but not glial fibrillary acidic protein is a potential biomarker of overt hepatic encephalopathy in patients with cirrhosis

Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigate...

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Published inAnnals of hepatology Vol. 29; no. 3; p. 101496
Main Authors de Wit, Koos, van Doorn, Diederick J., Mol, Bregje, van Vught, Lonneke A., Nevens, Frederik, Beuers, Ulrich, Ponsioen, Cyriel Y., Teunissen, Charlotte E., Takkenberg, R. Bart
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Published Mexico Elsevier España, S.L.U 01.05.2024
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Abstract Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE). We included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays. ICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each). Plasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.
AbstractList Introduction and Objectives: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE). Materials and Methods: We included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays. Results: ICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each). Conclusions: Plasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.
Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE). We included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays. ICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each). Plasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.
INTRODUCTION AND OBJECTIVESHepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE).MATERIALS AND METHODSWe included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays.RESULTSICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each).CONCLUSIONSPlasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.
ArticleNumber 101496
Author Beuers, Ulrich
Ponsioen, Cyriel Y.
de Wit, Koos
van Doorn, Diederick J.
van Vught, Lonneke A.
Nevens, Frederik
Mol, Bregje
Teunissen, Charlotte E.
Takkenberg, R. Bart
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  givenname: Charlotte E.
  orcidid: 0000-0002-4061-0837
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  organization: Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam, The Netherlands
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Issue 3
Keywords PSC
Liver diseases
Neuroproteins
Simoa
mHE
Metabolism
oHE
GFAP
MELD
NfL
CSF
ICU
HE
Brain diseases
TIPS
Language English
License This is an open access article under the CC BY-NC-ND license.
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Snippet Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of...
INTRODUCTION AND OBJECTIVESHepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can...
Introduction and Objectives: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can...
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SubjectTerms Adult
Aged
Biomarkers - blood
Brain diseases
Case-Control Studies
Female
Glial Fibrillary Acidic Protein - blood
Hepatic Encephalopathy - blood
Hepatic Encephalopathy - diagnosis
Hepatic Encephalopathy - etiology
Humans
Liver Cirrhosis - blood
Liver Cirrhosis - complications
Liver Cirrhosis - diagnosis
Liver diseases
Male
Metabolism
Middle Aged
Neurofilament Proteins - blood
Neuroproteins
Predictive Value of Tests
Prospective Studies
Severity of Illness Index
Title Neurofilament light chain but not glial fibrillary acidic protein is a potential biomarker of overt hepatic encephalopathy in patients with cirrhosis
URI https://dx.doi.org/10.1016/j.aohep.2024.101496
https://www.ncbi.nlm.nih.gov/pubmed/38460714
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