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

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Titel: The association of semaphorins 3C, 5A and 6D with liver fibrosis stage in chronic hepatitis C
Autoren: Neven Papic, Snjezana Zidovec Lepej, Lana Gorenec, Ivana Grgic, Slavko Gasparov, Tajana Filipec Kanizaj, Adriana Vince
Quelle: PLoS One
PLoS ONE, Vol 13, Iss 12, p e0209481 (2018)
Verlagsinformationen: Public Library of Science (PLoS), 2018.
Publikationsjahr: 2018
Schlagwörter: Liver Cirrhosis, Male, 0301 basic medicine, Semaphorins/blood, Nerve Tissue Proteins/metabolism, Hepacivirus, Semaphorins, Biomarkers/metabolism, Severity of Illness Index, Liver/immunology, Hepacivirus/isolation & purification, Liver Cirrhosis/immunology, Membrane Proteins/immunology, Prospective Studies, semaphorins 3C, liver fibrosis, Antiviral Agents/therapeutic use, 0303 health sciences, Liver Cirrhosis/blood, Middle Aged, 3. Good health, Nerve Tissue Proteins/immunology, Treatment Outcome, Liver, Disease Progression, Medicine, Female, Liver/pathology, Hepatitis C, Chronic/blood, Research Article, Liver/metabolism, Adult, Genotype, Science, Hepacivirus/genetics, Nerve Tissue Proteins, semaphorins 3C, 5A and 6D, liver fibrosis, chronic hepatitis C, Antiviral Agents, 03 medical and health sciences, Hepatitis C, Chronic/drug therapy, Semaphorins/immunology, Hepatitis C, Chronic/virology, 5A and 6D, Hepacivirus/immunology, chronic hepatitis C, Humans, Hepatitis C, Chronic/pathology, Nerve Tissue Proteins/blood, Aged, Membrane Proteins/blood, Membrane Proteins, Hepatitis C, Chronic, Liver Cirrhosis/virology, Membrane Proteins/metabolism, Semaphorins/metabolism, Liver Cirrhosis/diagnosis, Biomarkers/blood, Biomarkers
Beschreibung: 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.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0209481
Zugangs-URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0209481&type=printable
https://pubmed.ncbi.nlm.nih.gov/30592759
https://doaj.org/article/8b39784ef9044d4f97c0409f80264ed9
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310274/pdf/pone.0209481.pdf
https://doi.org/10.1371/journal.pone.0209481
https://europepmc.org/abstract/MED/30592759
https://dx.plos.org/10.1371/journal.pone.0209481
https://www.ncbi.nlm.nih.gov/pubmed/30592759
https://pubmed.ncbi.nlm.nih.gov/30592759/
https://www.bib.irb.hr/1000382
https://urn.nsk.hr/urn:nbn:hr:105:061232
https://doi.org/doi:10.1371/journal.pone.0209481
http://doi.org/10.1371/journal.pone.0209481
Rights: CC BY
URL: http://rightsstatements.org/vocab/InC/1.0/
Dokumentencode: edsair.doi.dedup.....a9e20c47bda604be1b075f1640e8b569
Datenbank: OpenAIRE
Beschreibung
Abstract: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.
ISSN:19326203
DOI:10.1371/journal.pone.0209481