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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-αand 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 TIMF-α, IL-1β, TGF-αand c-myc in liver specimens was detected by semi-quantitative comparative RT-PCR. RESULTS: TNF-αlevels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1βwas higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-αand staging (P=0.05) and between IL-1βlevels 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-αexpression and HCV genotype (P=0.02). CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-αlevels. As HCV-related liver damage progresses, TNF-αlevels drop while IL-1βand c-myc levels increase, which may be relevant to liver carcinogenesis.
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-α 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 TIMF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semi-quantitative comparative RT -PCR. RESULTS: TNF-alphalevels were significantly higher in hepatitis patients than in cirrhosis patients (P = 0.05). IL-1beta was higher in cirrhosis patients (P = 0.05) 0.05) and between IL-1βlevels and grading (P = 0.04). C-myc showed a significantly higher expression in cirrhosis patients (P = 0.001) ge 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 TNF-αexpression and HCV genotype (P = 0.02). CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-αlevels. As HCV-related liver damage progresses, TNF-αlevels drop while IL-1βand c-myc levels increase, which may be relevant to liver carcinogenesis.