The association of semaphorins 3C, 5A and 6D with liver fibrosis stage in chronic hepatitis C

Papić, Neven and Židovec Lepej, Snježana and Gorenec, Lana and Grgić, Ivana and Gašparov, Slavko and Filipec Kanižaj, Tajana and Vince, Adriana (2018) The association of semaphorins 3C, 5A and 6D with liver fibrosis stage in chronic hepatitis C. PLOS ONE, 13 (12). e0209481. ISSN 1932-6203

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Semaphorins are a diverse family of immunoregulators recently recognized to play a major role in various phases of immune responses. Their role in chronic viral hepatitis C (CHC) and contribution to the progression of liver disease is unknown. The aim of this study was to analyse the association of secreted semaphorins with the severity of liver disease in patients with CHC. Serum concentrations of semaphorins were measured in 114 treatment-naive CHC patients and 36 healthy controls. Serum concentrations of SEMA3A, SEMA3C, SEMA5A, SEMA6B and SEMA6D were significantly increased in patients with CHC compared to controls. While serum concentrations of SEMA3C and SEMA6D significantly increased with fibrosis stage in both HCV-g1 and HCV-g3 infections, the concentration of SEMA5A inversely correlated with fibrosis stage in both HCV genotypes. ROC analysis showed that serum concentrations of SEMA3C (>4.0ng/mL, AUC 0.88) and SEMA6D (>4.5, AUC 0.82) had higher AUC than widely used APRI (AUC 0.71) and FIB-4 (AUC 0.74) scores. Serum concentrations of SEMA3C and SEMA6D significantly decreased after DAA and PEG IFN-α/ribavirin therapy, while the serum concentration of SEMA5A significantly increased after DAAs therapy. Immunohistochemistry confirmed the expression of SEMA3C and SEMA5A in hepatocytes, endothelial cells and lymphocytes of cirrhotic livers from CHC patients but not in controls. In conclusion, we provide the first evidence that SEMA3C, SEMA5A and SEMA6D can be considered as markers of liver injury in CHC.

Item Type: Article
Additional Information: Copyright: © 2018 Papic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
MeSH: Adult ; Aged ; Antiviral Agents/therapeutic use ; Biomarkers/blood ; Biomarkers/metabolism ; Disease Progression ; Female ; Genotype ; Hepacivirus/genetics ; Hepacivirus/immunology ; Hepacivirus/isolation & purification ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/pathology ; Hepatitis C, Chronic/virology ; Humans ; Liver/immunology ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/blood ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/immunology ; Liver Cirrhosis/virology ; Male ; Membrane Proteins/blood ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Middle Aged ; Nerve Tissue Proteins/blood ; Nerve Tissue Proteins/immunology ; Nerve Tissue Proteins/metabolism ; Prospective Studies ; Semaphorins/blood ; Semaphorins/immunology ; Semaphorins/metabolism ; Severity of Illness Index ; Treatment Outcome
Departments: Katedra za infektologiju
Katedra za internu medicinu
Katedra za patologiju
Depositing User: Anja Majstorović
Status: Published
Židovec Lepej, SnježanaUNSPECIFIED
Gašparov, SlavkoUNSPECIFIED
Filipec Kanižaj, TajanaUNSPECIFIED
Date: 28 December 2018
Date Deposited: 07 Jun 2019 07:28
Last Modified: 14 Oct 2019 11:35
Subjects: /
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