Chronic infection with HBV has been reported to be associated with the development of HCC. The inflammation mounted by cytokine mediated immune system plays an important role in the pathogenesis of HBV associated HCC. IL-18 is a pro-inflammatory cytokine whose role in the development of HBV associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18 and expression level of

more »

... its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR-RFLP. Genotypic distributions between the groups were compared using odd's ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression level of pSTAT1 and pNFƙB were determined by western blotting. In case of IL-18(-607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(-137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were significantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT1 and pNF-κB) of IL-18 in stimulated PBMCs were significantly increased during HBV to HCC disease progression. These findings suggest that IL-18 has the potential to act as a biomarker of HBV related disease progression to HCC.