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

Scientific paper - Original scientific paper

• Author: Neven Papić
• Author: Snježana Židovec Lepej
• Author: Lana Gorenec
• Author: Ivana Grgić
• Author: Slavko Gašparov
• Author: Tajana Filipec Kanižaj
• Author: Adriana Vince
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

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.

• Keywords (english): 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
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: PLOS ONE
• Numbering: vol. 13, no. 12, e0209481
• p-ISSN: 1932-6203
• DOI: https://doi.org/doi:10.1371/journal.pone.0209481
• URN:NBN: urn:nbn:hr:105:061232
• Publication: 2018-12-28
• Document URL: http://doi.org/10.1371/journal.pone.0209481
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 09:54:03