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Serum sphingolipids predict de novo hepatocellular carcinoma in hepatitis C cirrhotic patients with sustained virologic response.

Authors
  • Mücke, Victoria T1
  • Thomas, Dominique2
  • Mücke, Marcus M1
  • Waidmann, Oliver1
  • Zeuzem, Stefan1
  • Sarrazin, Christoph1, 3
  • Pfeilschifter, Josef4
  • Vermehren, Johannes1
  • Finkelmeier, Fabian1
  • Grammatikos, Georgios1, 5
  • 1 Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. , (Germany)
  • 2 Pharmazentrum Frankfurt, Institut für Klinische Pharmakologie, Frankfurt am Main, Germany. , (Germany)
  • 3 St. Josefs-Hospital, Wiesbaden, Germany. , (Germany)
  • 4 Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Frankfurt am Main, Germany. , (Germany)
  • 5 St. Luke's Hospital Thessaloniki, Panorama, Greece. , (Greece)
Type
Published Article
Journal
Liver international : official journal of the International Association for the Study of the Liver
Publication Date
Nov 01, 2019
Volume
39
Issue
11
Pages
2174–2183
Identifiers
DOI: 10.1111/liv.14178
PMID: 31207039
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Curing hepatitis C virus (HCV) infection reduces the risk of hepatocellular carcinoma (HCC) development, yet HCC occurs despite sustained virologic response (SVR) in 2%-8% of cirrhotic patients. Sphingolipids (SLs) have been identified as new biomarkers of chronic liver disease and HCC. The aim of this study was to evaluate serum SLs as diagnostic HCC biomarkers in patients with HCV-associated cirrhosis at SVR12. From 2014 to 2016, 166 patients with HCV-cirrhosis and SVR were recruited and SL profiles were measured at baseline and 12 weeks after completion of direct-acting antiviral (DAA) therapy. All patients received HCC surveillance in line with current guideline recommendations. Minimum follow-up period comprised 6 months. Our study included 130 (78%) patients without history of HCC, 25 (15%) with history of HCC prior DAA therapy and 11 (7%) patients with de novo HCC after FU12. In those with upcoming de novo HCC serum C24DHC (P = 0.006), C24:1DHC (P = 0.048) and C16Cer (P = 0.011) were significantly upregulated at FU12, but not AFP (P = 0.138). Contemporaneous ultrasound did not visualize HCC, at this time. C16Cer stayed sole independent predictor with high diagnostic accuracy of AFP-positive (AUC = 0.741) and -negative (AUC = 0.766) HCC development. Serum SL parameters decreased from baseline to SVR12. C24DHC, C24:1DHC and especially C16Cer were superior to AFP in early detection of AFP-positive and -negative de novo HCC development. We observed significant SL profile changes upon SVR. SLs may play a role in non-invasive HCC surveillance and hepatocarcinogenesis. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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