Farinati Fabio, Cardin Romilda, Bortolami Marina, Guido Maria, Rugge Massimo
Department of Surgical and Gastroenterological Sciences, University of Padua, Italy.
World J Gastroenterol. 2006 Apr 7;12(13):2065-9. doi: 10.3748/wjg.v12.i13.2065.
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.
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.
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).
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.
评估慢性丙型肝炎病毒（HCV）相关肝炎中发生的氧化性DNA损伤与促炎细胞因子、转化生长因子-α（TGF-α）和c-myc表达水平之间是否存在相关性。
该系列研究纳入了37例慢性活动性HCV相关肝炎患者和11例HCV相关代偿性肝硬化患者。使用电化学检测器对肝活检组织中的8-羟基脱氧鸟苷进行定量。通过半定量比较逆转录聚合酶链反应（RT-PCR）检测肝标本中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、TGF-α和c-myc的mRNA表达。
肝炎患者的TNF-α水平显著高于肝硬化患者（P = 0.05）。肝硬化患者的IL-1β水平较高（P = 0.05）。发现TNF-α与分期之间存在显著相关性（P = 0.05），IL-1β水平与分级之间存在显著相关性（P = 0.04）。c-myc在肝硬化患者中的表达显著更高（P = 0.001）。肝硬化患者的8-羟基脱氧鸟苷水平显著更高（P = 0.05），HCV基因1型患者中也显著更高（P = 0.03）。在所有患者中，发现8-羟基脱氧鸟苷水平与基因型（P = 0.04）和分级（P = 0.007）相关。多因素逻辑回归分析也表明DNA加合物数量、TNF-α表达与HCV基因型之间存在显著相关性（P = 0.02）。
在慢性HCV相关肝损伤中，氧化性DNA损伤与HCV基因型、分级和TNF-α水平相关。随着HCV相关肝损伤的进展，TNF-α水平下降，而IL-1β和c-myc水平升高，这可能与肝癌发生有关。
