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.
Highlights
Since its discovery 30 years ago, chronic hepatitis C (CHC) has evolved from an incurable disease to the prototype of chronic viral infection that can be and safely cured
Paired samples before and 12 weeks after antiviral therapy were analyzed in 23 patients (14 treated with direct acting antivirals without interferon, and 9 patients treated with pegylated interferon alpha) that achieved sustained virological response (SVR, defined as undetectable HCV RNA at 12 weeks after the end of antiviral therapy). 36 voluntary blood donors without relevant medical history and without obesity, the use of medication and/ or alcohol abuse were included as healthy controls (HC)
The majority of CHC patients were infected with HCV genotype 1 (n = 70) and 44 patients were infected with genotype 3
Summary
Since its discovery 30 years ago, chronic hepatitis C (CHC) has evolved from an incurable disease to the prototype of chronic viral infection that can be and safely cured.
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