The potential value of plasma Circ-ITCH in hepatocellular carcinoma patients with current hepatitis C virus infection.

BACKGROUND: There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. Circular RNAs have recently attracted great interest as promising biomarkers and treatment targets. However, their function in hepatocellular carcinoma whose etiology related to hepatitis C has been rarely studied. AIM OF WORK: The current study was conducted to analyze differential expression of circ-ITCH in plasma of Egyptian HCC patients with concomitant HCV infection, compared to normal control subjects, to investigate its correlation with liver function parameters, and to determine the possible diagnostic ability of circ-ITCH in plasma as a non-invasive marker, compared to its linear counterpart. RESULTS: The results showed that the relative expression of circ-ITCH was significantly higher in the plasma of HCC patients (P<0.05). Moreover, when comparing its expression in the metastatic and non-metastatic subgroups, it was significantly higher in the non-metastatic HCC group compared to control group (P<0.05). Circ-ITCH was positively correlated with liver enzymes AST, ALT (P<0.001), also was significantly higher in HCC child C patients. To evaluate the potential diagnostic value of circ-ITCH in plasma, a ROC curve was generated, the AUC was 0.661, (95% CI: 0.5433-0.778) with a sensitivity and specificity 65% and 70% respectively. CONCLUSION: The results revealed that circ-ITCH is-with no doubt-involved in the pathogenesis of HCC and its high level may be related to HCV infection, further researches in this area will certainly make great contributions in understanding. In conclusion our results suggested that circ-ITCH may be used as a noninvasive diagnostic marker and a promising therapeutic target for HCC.

Alterations in serum levels of fetuin A and selenoprotein P in chronic hepatitis C patients with concomitant type 2 diabetes: A case-control study.

BACKGROUND: Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. However, the mechanism underlying the IR in chronic HCV is obscure. Hepatokines are group of liver-derived protein, which affect the glucose and lipid metabolism in several tissues. Fetuin A (also known as human α2-HS-glycoprotein) is one of the hepatokines, which was recognized as a natural inhibitor of the insulin receptor tyrosine kinase in liver and skeletal muscle. Additionally, selenoprotein P has emerged as an important hepatokine, which primarily acts as selenium transporter and has been reported to be implicated in glucose homeostasis in human. OBJECTIVE: The aim of the current case-control study was to investigate the serum levels of both fetuin A and selenoprotein P in chronic hepatitis C patients with or without T2DM and to correlate their levels with other biochemical parameters of insulin resistance. MAIN FINDINGS: Our results showed that, serum fetuin A levels increased significantly in HCV patients compared with controls (P<0.01) and surplus increase was found in HCV with concomitant T2DM (P>0.001). However, selenoprotein P levels significantly elevated only in patients with both HCV and T2DM (P<0.05) compared with the healthy subjects. Both fetuin A and selenoprotein P were positively correlated with fasting blood glucose. Yet, only fetuin A was significantly correlated to the HOMA-IR (r=0.28; P=0.03). CONCLUSIONS: These results indicate crucial roles played by fetuin A and selenoprotein P in the IR caused by HCV and that both hepatokines may be targets for the development of therapies to treat or inhibit insulin resistance associated to HCV. However, further studies on large scale should be conducted to confirm our findings.

The potential value of plasma Circ-ITCH in hepatocellular carcinoma patients with current hepatitis C virus infection / El valor potencial de Circ-ITCH en plasma en pacientes con carcinoma hepatocelular con infección actual por el virus de la hepatitis C

Background: There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. Circular RNAs have recently attracted great interest as promising biomarkers and treatment targets. However, their function in hepatocellular carcinoma whose etiology related to hepatitis C has been rarely studied. Aim of work: The current study was conducted to analyze differential expression of circ-ITCH in plasma of Egyptian HCC patients with concomitant HCV infection, compared to normal control subjects, to investigate its correlation with liver function parameters, and to determine the possible diagnostic ability of circ-ITCH in plasma as a non-invasive marker, compared to its linear counterpart. Results: The results showed that the relative expression of circ-ITCH was significantly higher in the plasma of HCC patients (P<0.05). Moreover, when comparing its expression in the metastatic and non-metastatic subgroups, it was significantly higher in the non-metastatic HCC group compared to control group (P<0.05). Circ-ITCH was positively correlated with liver enzymes AST, ALT (P<0.001), also was significantly higher in HCC child C patients. To evaluate the potential diagnostic value of circ-ITCH in plasma, a ROC curve was generated, the AUC was 0.661, (95% CI: 0.5433–0.778) with a sensitivity and specificity 65% and 70% respectively. Conclusion: The results revealed that circ-ITCH is-with no doubt-involved in the pathogenesis of HCC and its high level may be related to HCV infection, further researches in this area will certainly make great contributions in understanding. In conclusion our results suggested that circ-ITCH may be used as a noninvasive diagnostic marker and a promising therapeutic target for HCC.(AU)

Antecedentes: Existe una necesidad obvia de diagnosticar el carcinoma hepatocelular (CHC) utilizando nuevos biomarcadores no invasivos y sensibles. Los ARN circulares han atraído recientemente un gran interés como biomarcadores prometedores y dianas de tratamiento. Sin embargo, su función en el carcinoma hepatocelular, cuya etiología está relacionada con la hepatitis C, apenas ha sido estudiada. Objetivo: Este estudio se realizó para analizar la expresión diferencial de circ-ITCH en el plasma de pacientes egipcios con CHC con infección concomitante por VHC, en comparación con sujetos de control normales, para investigar su correlación con los parámetros de la función hepática y para determinar la posible capacidad diagnóstica de circ-ITCH en plasma como marcador no invasivo, en comparación con su contraparte lineal. Resultados: Los resultados mostraron que la expresión relativa de circ-ITCH fue significativamente mayor en el plasma de pacientes con CHC (p<0,05). Además, al comparar su expresión en los subgrupos metastásico y no metastásico, fue significativamente mayor en el grupo de CHC no metastásico en comparación con el grupo control (p<0,05). Circ-ITCH se correlacionó positivamente con las enzimas hepáticas AST y ALT (p<0,001), y también fue significativamente mayor en pacientes con CHC infantil con VHC. Para evaluar el valor diagnóstico potencial de circ-ITCH en plasma se generó una curva ROC, el AUC fue de 0,661 (IC95%: 0,5433-0,778), con una sensibilidad y una especificidad del 65% y del 70%, respectivamente. Conclusión: Los resultados revelaron que circ-ITCH está, sin duda, involucrado en la patogénesis del CHC, y su alto nivel puede estar relacionado con la infección por VHC, por lo que investigaciones adicionales en esta área ciertamente harán grandes contribuciones para su comprensión. En conclusión, nuestros resultados sugirieron que circ-ITCH puede usarse como un marcador de diagnóstico no invasivo y una diana terapéutica prometedora para el CHC.(AU)