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

Znanstveni rad - Izvorni znanstveni rad

• Autor: Neven Papić
• Autor: Snježana Židovec Lepej
• Autor: Lana Gorenec
• Autor: Ivana Grgić
• Autor: Slavko Gašparov
• Autor: Tajana Filipec Kanižaj
• Autor: Adriana Vince
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti

Sažetak (engleski)

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.

• Ključne riječi (engleski): 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
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: PLOS ONE
• Brojčani podaci: vol. 13, br. 12, e0209481
• p-ISSN: 1932-6203
• DOI: https://doi.org/doi:10.1371/journal.pone.0209481
• URN:NBN: urn:nbn:hr:105:061232
• Datum objave publikacije: 2018-12-28
• URL dokumenta: http://doi.org/10.1371/journal.pone.0209481
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-03-28 09:54:03