Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels.
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.
Pharmazentrum Frankfurt, Institut f&#252;r Allgemeine Pharmakologie, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. georgios.grammatikos@kgu.de.|Medizinische Klinik 1, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. georgios.grammatikos@kgu.de.
Georgios
G
Grammatikos
Medizinische Klinik 1, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. julia.dietz@em.uni-frankfurt.de.
Julia
J
Dietz
Pharmazentrum Frankfurt, Institut f&#252;r klinische Pharmakologie, Goethe University Hospital, 60590 Frankfurt am Main, Germany. ferreirosbouzas@em.uni-frankfurt.de.
Nerea
N
Ferreiros
Pharmazentrum Frankfurt, Institut f&#252;r Allgemeine Pharmakologie, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Koch@med.uni-frankfurt.de.
Alexander
A
Koch
Medizinische Klinik 1, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. georg.dultz@kgu.de.
Georg
G
Dultz
Institute of Biostatistics and Mathematical Modelling, Department of Medicine, Goethe University, 60590 Frankfurt am Main, Germany. bon@med.uni-frankfurt.de.
Dimitra
D
Bon
Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece. karakasiliotis@pasteur.gr.
Ioannis
I
Karakasiliotis
Infektiologikum, 60590 Frankfurt am Main, Germany. lutz@infektiologikum.de.
Thomas
T
Lutz
Infektiologikum, 60590 Frankfurt am Main, Germany. knecht@infektiologikum.de.
Gaby
G
Knecht
Infektiologikum, 60590 Frankfurt am Main, Germany. gute@infektiologikum.de.
Peter
P
Gute
Pharmazentrum Frankfurt, Institut f&#252;r klinische Pharmakologie, Goethe University Hospital, 60590 Frankfurt am Main, Germany. Herrmann@med.uni-frankfurt.de.
Eva
E
Herrmann
Medizinische Klinik 1, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. zeuzem@em.uni-frankfurt.de.
Stefan
S
Zeuzem
Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece. penelopm@pasteur.gr.|Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece. penelopm@pasteur.gr.
Penelope
P
Mavromara
Medizinische Klinik 1, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. sarrazin@em.uni-frankfurt.de.
Christoph
C
Sarrazin
Pharmazentrum Frankfurt, Institut f&#252;r Allgemeine Pharmakologie, Goethe University Hospital, Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. pfeilschifter@em.uni-frankfurt.de.
Josef
J
Pfeilschifter
D000328:Adult; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D002518:Ceramides / Q000378:metabolism*; D060085:Coinfection; D005260:Female; D005838:Genotype; D015658:HIV Infections; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood*; D019562:Viral Load; D055815:Young Adult
C479896:ANGPTL3 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000998:Antiviral Agents; D015415:Biomarkers; D002518:Ceramides; D013110:Sphingosine; C005682:safingol
HIV; angiopoietin-like 3 (ANGPTL3); biomarker; hepatitis C; sphingolipid