The role of serum sphingolipids as potential biomarkers of non-response to direct acting antiviral therapy in chronic hepatitis C virus infection.
Humans
Hepatitis C, Chronic
/ drug therapy
Antiviral Agents
/ therapeutic use
Sphingolipids
/ therapeutic use
Sphingosine
/ therapeutic use
Retrospective Studies
Chromatography, Liquid
Tandem Mass Spectrometry
Hepatitis C
/ drug therapy
Hepacivirus
/ physiology
Sustained Virologic Response
Biomarkers
antiviral agents
biomarkers
hepatitis C
sphingolipids
sustained virological response
Journal
Journal of viral hepatitis
ISSN: 1365-2893
Titre abrégé: J Viral Hepat
Pays: England
ID NLM: 9435672
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
07
11
2022
received:
22
08
2022
accepted:
14
11
2022
pubmed:
5
12
2022
medline:
20
1
2023
entrez:
4
12
2022
Statut:
ppublish
Résumé
Elimination strategies of chronic hepatitis C virus (HCV) infection aim to optimize the high antiviral potency of direct-acting antivirals (DAAs). Sphingolipids (SLs) constitute bioactive lipid compounds with a remarkable second messenger potential. SL levels associate with responsiveness to interferon treatment in HCV-patients, thus prompting the question whether failure to DAAs can be predicted by the serologic sphingolipidomic profile. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to retrospectively quantify various sphingolipid metabolites in baseline serum samples of 97 chronic HCV patients with DAA failure compared with an age-matched cohort of 95 HCV-patients with sustained virological response (SVR). Sphingosine, sphinganine, sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (SA1P) serum concentrations were significantly upregulated at baseline in patients with DAA failure compared to patients with SVR. Similarly, GluC24:1Cer baseline levels were significantly upregulated in patients with DAA failure compared to the patients with SVR. However, GluC18Cer serum levels showed decreased baseline levels for patients with DAA failure compared to patients with SVR. In multivariate analysis sphinganine (OR 0.08494, CI 0.07393-0.9759, p = .021223), SA1P (OR 0.9818, CI 0.9653-0.9987, p = .034801), GluCerC18 (OR 1.0683, CI 1.0297-1.1104, p = .000786) and GluCer24:1 (OR 0.9961, CI 0.994-0.998, p = .000294) constituted independent predictors of treatment response. In conclusion, serum sphingolipid concentrations, in particular sphingosine, sphinganine and their derivatives S1P and SA1P as well as glucosylceramides may identify at baseline the minority of HCV patients with DAA failure. Serum sphingolipids could constitute additional biomarkers for national treatment strategies aiming to eliminate HCV infection.
Substances chimiques
Antiviral Agents
0
Sphingolipids
0
safingol
OWA98U788S
sphingosine 1-phosphate
26993-30-6
dihydrosphingosine 1-phosphate
19794-97-9
Sphingosine
NGZ37HRE42
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-147Informations de copyright
© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.
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