Oxidative damage, pro-inflammatory cytokines, TGF-alpha and c-myc in chronic HCV-related hepatitis and cirrhosis.
OBJECTIVE
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-1beta, TGF-alpha and c-myc in liver specimens was detected by semi-quantitative comparative RT-PCR.


RESULTS
TNF-alpha levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1beta was higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-alpha and staging (P=0.05) and between IL-1beta 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).


CONCLUSIONS
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-1beta and c-myc levels increase, which may be relevant to liver carcinogenesis.
Farinati
Fabio
F
Department of Surgical and Gastroenterological Sciences, University of Padua, Italy. fabio.farinati@unipd.it
Cardin
Romilda
R
Bortolami
Marina
M
Guido
Maria
M
Rugge
Massimo
M
D000328:Adult; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics*; D004249:DNA Damage; D005260:Female; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D016211:Transforming Growth Factor alpha / Q000235:genetics*
D016207:Cytokines; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha