Oxidative damage, pro-inflammatory cytokines, TGF-alpha and c-myc in chronic HCV-related hepatitis and cirrhosis.

Abstract: Aim: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-alpha and c-myc. Methods: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-alpha, IL-1 beta, TGF-alpha and c-myc in liver specimens was detected by semiquantitative comparative RT-PCR. Results: TNF-alpha levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1 beta was higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-alpha and staging (P=0.05) and between IL-1 beta levels and grading (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-alpha expression and HCV genotype (P=0.02). Conclusion: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-alpha levels. As HCV-related liver damage progresses, TNF-alpha levels drop while IL-1 beta and c-myc levels increase, which may be relevant to liver carcinogenesis.