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World J Gastroenterol. Apr 7, 2006; 12(13): 2065-2069
Published online Apr 7, 2006. doi: 10.3748/wjg.v12.i13.2065
Oxidative damage, pro-inflammatory cytokines, TGF-α and c-myc in chronic HCV-related hepatitis and cirrhosis
Fabio Farinati, Romilda Cardin, Marina Bortolami, Maria Guido, Massimo Rugge
Fabio Farinati, Romilda Cardin, Marina Bortolami, Department of Surgical and Gastroenterological Sciences, University of Padua, Italy
Maria Guido, Massimo Rugge, Department of Oncological and Surgical Sciences, University of Padua, Italy
Author contributions: All authors contributed equally to the work.
Supported by PRIN grants from the Italian Ministry of Science and Technology, No. 2003063143-006
Correspondence to: Fabio Farinati, MD, Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Sezione di Gastroenterologia, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy. fabio.farinati@unipd.it
Telephone: +39-49-8211305 Fax: +39-49-8760820
Received: January 18, 2005
Revised: June 6, 2005
Accepted: June 18, 2005
Published online: April 7, 2006
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-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 TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semi-quantitative comparative RT-PCR.

RESULTS: TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients (P = 0.05). IL-1β was higher in cirrhosis patients (P = 0.05). A significant correlation was found between TNF-α and staging (P = 0.05) and between IL-1β 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-α expression and HCV genotype (P = 0.02).

CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.

Keywords: Oxidative DNA damage; Chronic HCV-related hepatitis; Inflammatory mediators