Telomerase Expression Related with Poor Immune Response to HCV Core Antigen in Egyptian HCV Patients’ PBMCs

Abstract Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. This study aimed to assess serum hTERT level and its relation to the progression of liver disease. Also, it aimed to assess the effect of HCV core protein on memory T-cells in HCV patients with or without HCC, and the correlation between memory cells phenotype and the progression of the disease in the same patients. hTERT level in serum was assessed through relative quantitative RT-PCR. Flow cytometric analysis was used to assess T-cells responsiveness (as IFN-γ secretion) before and after stimulation with HCV core protein, and memory CD8+ cells phenotype using several differentiation markers. hTERT was found to be increased in a stepwise manner upon comparing its level in controls, chronic hepatitis patients, cirrhotic patients, and HCC patients. T-cells showed a similar manner of stepwise decrease in response (decreased IFN-γ secretion) in HCC patients compared to HCV patients without HCC and controls. Also, late differentiated memory cells (CD8+ CD27- CD28- CD45RA+CCR7-) were depleted in HCC patients compared to HCV patients without HCC. In conclusion, these results suggest a negative correlation between hTERT and IFN-γ secretion by T- cells in HCV patients and that this relationship along with the depletion of late differentiated memory cells could help the progression of liver disease to HCC.