engleski

Increased expression of semaphorin 3c and 6b in chronic hepatitis C is associated with the severity of liver disease

Background: Semaphorins are a diverse family of biological modifiers that are important for the development and function of neurological, immune, cardiovascular and respiratory systems. Semaphorins are involved in a series of immune cell interactions, which ultimately influence the outcome of the immune response by amplifying inflammation while dampening T-cell proliferation and activation. Their role in chronic hepatitis C (CHC) and contribution to the progression of liver disease is unknown. Here we examined the association of semaphorin-3C (SEMA3C, possible controller of angiogenesis and T-cell proliferation) and -6B (SEMA6B, possible regulator of interferon signalling) with the severity of liver disease in CHC patients. Material/methods: Serum concentrations of SEMA3C and SEMA6B were measured in 58 treatmentnaive CHC patients (51.6±11.4 years, 31 males) and in 12 healthy controls (52.6±18.1 years, 5 males). Semaphorin concentration was analysed according to the stage of fibrosis (as measured by METAVIR), HCV genotype/subtype infection and clinical and biochemical parameters. Results: The majority of CHC patients were infected with HCV genotype 1 (HCV-g1a n=20 ; HCV-g1b n=18 ; subtype undetermined n=4) and 16 patients were infected with genotype 3. CHC patients were classified into four groups according to the Metavir score (Metavir 1 n=12 ; Metavir 2 n=12, Metavir 3 n=14, Metavir 4 n=20). Serum concentrations of SEMA3C were significantly higher in patients with HCV-g1 and HCV-g3 infection as compared with controls (4.36±0.86 ng/mL, 4.82±0.66 ng/mL, 2.79±1.03 ng/mL, Prespectively, p<0.001). SEMA3C concentration significantly correlated with fibrosis stage, both in HCV-g1 (F1 4.03±0.52ng/mL, p=0.004 ; F2, 3.58±0.41ng/mL, p=0.026 ; F3 4.79±0.87ng/mL p<0.0001 ; F4 4.72±0.83, p<0.0001) and HCV-g3 infection (F1 4.03±0.59ng/mL, p=0.021 ; F2 4.63±0.36ng/mL, p=0.021 ; F3 5.15±0.47ng/mL, p=0.002, F4 4.12±0.58, p<0.0001). SEMA3C concentration correlated with age (r=0.39, p=0.014), FIB-4 (r=0.49, p=0.005) and METAVIR score (r=0.43, p=0.005) and Platelet count (r=-0.36, p=0.033). Similarly, serum concentrations of SEMA6B were significantly higher in patients with HCV-g1 and HCV-g3 infection as compared with controls (3.92±3.46 ng/mL, 3.88±2.35 ng/mL, 1.71±0.99ng/mL, respectively p<0.001). Interestingly, concentrations of SEMA6B decreased with fibrosis stage (F1 3.53±1.99ng/mL vs. F4 2.55±4, 55ng/mL, p=0.05) in HCV-g1 infection, but increased with fibrosis in HCV-g3 infection (F1 2.54±0.40ng/mL vs. F4 4.83±3.03ng/mL). Accordingly, in HCV-g1 infection SEMA6B concentration correlated with platelet count (r=0.37, p=0.026), and inversely correlated with METAVIR (r=-0.35, p=0.027). According to the ROC analysis (Figure 1), serum concentrations of SEMA3C showed superior sensitivity and specificity for detection of liver cirrhosis (>4.0, sensitivity 84.6%, specificity 74.3%, p<0.001, AUC 0.84), as compared to widely used APRI score (>1.4 sensitivity 66.7%, specificity 67.7%, p=0.0508, AUC 0.65) or FIB-4 score (>2.4 sensitivity 72.2%, specificity 77.5%, p=0.0015 AUC 0.75). Conclusions: These results indicate that SEMA3C and SEMA6B are involved in immune response to chronic HCV infection. Since their concentration correlates with the extent of liver disease, they might be considered as new biomarkers of liver fibrogenesis.

Semaphorin ; chronic hepatitis C ; liver disease

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