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Int. J. Mol. Sci. 2016, 17(6), 922; doi:10.3390/ijms17060922

Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels

1
Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
2
Medizinische Klinik 1, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
3
Pharmazentrum Frankfurt, Institut für klinische Pharmakologie, Goethe University Hospital, 60590 Frankfurt am Main, Germany
4
Institute of Biostatistics and Mathematical Modelling, Department of Medicine, Goethe University, 60590 Frankfurt am Main, Germany
5
Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece
6
Infektiologikum, 60590 Frankfurt am Main, Germany
7
Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece
*
Author to whom correspondence should be addressed.
Academic Editor: Johannes Haybaeck
Received: 14 May 2016 / Revised: 27 May 2016 / Accepted: 31 May 2016 / Published: 13 June 2016
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
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Abstract

Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations. View Full-Text
Keywords: HIV; hepatitis C; sphingolipid; biomarker; angiopoietin-like 3 (ANGPTL3) HIV; hepatitis C; sphingolipid; biomarker; angiopoietin-like 3 (ANGPTL3)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Grammatikos, G.; Dietz, J.; Ferreiros, N.; Koch, A.; Dultz, G.; Bon, D.; Karakasiliotis, I.; Lutz, T.; Knecht, G.; Gute, P.; Herrmann, E.; Zeuzem, S.; Mavromara, P.; Sarrazin, C.; Pfeilschifter, J. Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels. Int. J. Mol. Sci. 2016, 17, 922.

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