Abstract
The role of growth factors produced by the liver, including insulin-like growth factor-1 (IGF-1) and its main binding protein, IGF binding protein-3 (IGFBP-3), in hepatitis C virus (HCV)-associated carcinogenesis has only partially been recognized and there is not much data available on the local expression of IGF-1 and IGFBP-3 in chronic hepatitis C (CH‑C). Therefore, the aim of the present study was to evaluate the IGF‑1 and IGFBP‑3 serum levels and tissue expression in liver biopsies of CH‑C patients (n=37) and hepatocellular carcinoma (HCC) samples (n=61) as related to age- and gender-matched control serum samples (n=15) and healthy liver samples (n=10). Serum concentrations of IGF-1 (S-IGF-1) and IGFBP‑3 (S-IGFBP‑3) were measured by the ELISA method. Tissue expression of proteins was detected using ABC immunocytochemistry and evaluated applying a spatial visualization technique. Concentrations of S-IGF-1 and hepatic expression of IGF-1 (H-IGF-1) proved to be lower in CH-C compared to the controls. No significant differences were detected in the concentration of S-IGFBP-3 between the studied groups but the S-IGF-1/IGFBP-3 ratio in the CH-C group was significantly lower compared to the control. H-IGFBP-3 was higher in CH-C compared to those in the control and HCC. In HCC, lower expression of H-IGF-1 was detected compared to the control and a higher H-IGF-1/IGFBP-3 ratio compared to CH-C. A negative correlation was detected between S-IGF-1 and S-IGF-1/IGFBP-3 ratio, on the one hand, and age, grading and concentration of α-fetoprotein (AFP) on the other, while H-IGFBP-3 was negatively correlated with BMI in the CH‑C group. In patients with CH‑C, the H‑IGF‑1/IGFBP‑3 ratio was higher compared to that of the S‑IGF‑1/IGFBP‑3 ratio. The studies documented a disturbed H‑IGF‑1 and H‑IGFBP‑3 in CH‑C, which may be of significance in carcinogenesis. Examination of serum concentration and tissue expression of the two proteins and, first of all, estimation of the IGF‑1/IGFBP‑3 ratio may provide additional (to the estimation of IGF‑1 and AFP) non-invasive markers in HCV‑related liver injury.
Highlights
Infection with hepatitis C virus (HCV) leads to chronic hepatitis in 60‐80% of the patients, with the exception of individuals infected with genotype 2 in Africa, who were found to eliminate the virus more effectively (~50% of the cases)
In the Chronic hepatitis C (CH-C) group, our investigations confirmed the negative correlation between concentration of S-insulin-like growth factor-1 (IGF-1) and patient age described by other authors [43,44]
In the CH-C group, we demonstrated that mean Serum concentrations of insulin-like growth factor (IGF)-1 (S-IGF-1) concentration is higher in women as compared to men
Summary
Infection with hepatitis C virus (HCV) leads to chronic hepatitis in 60‐80% of the patients, with the exception of individuals infected with genotype 2 in Africa, who were found to eliminate the virus more effectively (~50% of the cases). In HCV-related carcinogenesis, participation of viral proteins themselves used to be accentuated, including at least three HCV proteins: capsid protein (core, protein C) and two non-structural proteins, NS3 and NS5A [4,5]. Such products of HCV genome have a direct influence on the disturbance of balance between proliferation and apoptosis of liver cells. These processes are regulated by liver-derived growth factors, to which insulin-like growth factor (IGF)-1 and -2 belong [6,7].
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