RESUMO
Hepatitis C virus [HCV] infection represents a serious threat to human health; often resulting in liver cirrhosis and hepatocellular carcinoma [HCC]. The exact mechanisms responsible for persistent infection and long -term hepatocellular injury are poorly understood. It is hypothesized that the pro-inflammatory cytokine IL-18 may have an important role in chronic cellular immune response towards hepatocytes in the course of the disease. Of this study was to evaluate the significance of measuring IL-18 mRNA in peripheral blood mononuclear cells [PBMCs] in viral hepatitis C patients with chronic infection and HCC. Forty selected patients with chronic HCV infection [12 with compensated liver functions "group I" ; 12 with decompensated liver functions "group II"; and 16 with HCC on top of chronic HCV infection "group III"] and 10 healthy controls with matched ages and sex were studied. Using reverse- transcriptase polymerase chain reaction [RT-PCR], detection of HCVRNA in blood of patients and quantitation of IL-18 mRNA transcripts in PBMCs of patients and control were performed. This study showed a significant increase [p<0.001] in the mean value of transcriptional expression of IL-18 gene [as a ratio to that of beta-globin] in PBMCs in all patients groups compared to control. A positive [however insignificant] correlation was detected between transcriptional expression of IL-18 gene and serum albumin [r=0.446]; ALT[r=0.074] as well as prothrombin time [r=0.332] in chronic viral hepatitis patient groups [compensated and decompensated]. A significant positive correlation was found between transcriptional expression of IL-18 gene and hepatitis C viral load in all patient groups[r=0.756; 0.669; and 0.956 respectively]. These results support the hypothesis that IL-18 has an important role in the immunopathogenetic events leading to liver injury in chronic HCV infection. The antiviral action of IL-18 might be counteracted by multiple factors leading to persistent HCV infection [as IL-10]. The question becomes important whether and to what extent the HCC is influenced by IL-18. Future follow- up studies are recommended to investigate the role of monoclonal antibody to IL-18 in amelioration of liver damage and cirrhosis in such patients, in addition to further studies to highlight the role of IL-18 binding protein [BP] and Th-2 cytokines [as IL-10] as possible antagonists to the antiviral action of IL-18. Finally future- large scales studies correlating IL-18 gene expression with markers of HCC progression are recommended to gain insight into the antitumor action of IL-18 as it would be a promising new strategy to control HCC