Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C
Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C
复制标题
DOI：
10.1111/j.1365-2893.2008.00972.x
复制
发表时间：
2008-07-01
影响因子：
2.5
通讯作者：
Takei, Y.
中科院分区：
文献类型：
--
作者：
Fujita, N.;Sugimoto, R.;Takei, Y.
8-羟基脱氧鸟苷（8-OHdG）是一种由羟基自由基引起的DNA损伤，被认为是评估氧化应激诱导的DNA损伤的有用标志物。本研究旨在阐明慢性病毒性肝炎患者肝脏8-OHdG水平的临床意义。通过肝活检标本的免疫组织化学染色，研究了慢性丙型肝炎（CH-C）（n = 77）和慢性B肝炎（CH-B）（n = 34）患者的肝脏8-OHdG蓄积。8-CH-C患者的OHdG阳性肝细胞显著高于CH-B患者（中位数55.0 vs 18.8 cells/10（5）mu m（2），P < 0.0001）。随着血清转氨酶水平的升高，阳性肝细胞数明显增加，尤其是CH-C患者（8-OHdG与丙氨酸转氨酶（ALT）/天冬氨酸转氨酶（AST）的相关系数分别为0.738/0.720和0.506/0.515）。8-在CH-C中，OHdG反应性与身体和肝脏铁储存标志物密切相关（与血清铁蛋白，r = 0.615;与肝脏总铁评分，r = 0.520;与肝脏hepcidin mRNA水平，r = 0.571），尽管它与CH-B中的血清HBV-DNA滴度（r = 0.540）和患者年龄（r = -0.559）相关。这些结果表明，肝DNA氧化损伤是常见的慢性病毒性肝炎，特别是慢性HCV感染的患者，这表明慢性肝脏炎症和肝癌发生之间可能存在联系。肝DNA损伤与铁超载之间的强正相关性表明，铁含量是最可能的肝脏氧化应激介质之一，减少铁可能有利于降低CH-C患者肝癌的发病率。
8-Hydroxydeoxyguanosine (8-OHdG) is a promutagenic DNA lesion produced by hydroxyl radicals and is recognized as a useful marker in estimating DNA damage induced by oxidative stress. The aim of this study was to clarify the clinical significance of hepatic 8-OHdG levels in patients with chronic viral hepatitis. Hepatic 8-OHdG accumulation was investigated in patients with chronic hepatitis C (CH-C) (n = 77) and chronic hepatitis B (CH-B) (n = 34) by immunohistochemical staining of liver biopsy samples. 8-OHdG positive hepatocytes were significantly higher in patients with CH-C compared to CH-B (median 55.0 vs 18.8 cells/10(5) mu m(2), P < 0.0001). The number of positive hepatocytes significantly increased with the elevation of serum aminotransferase levels, especially in CH-C patients (8-OHdG vs alanine aminotransferase (ALT)/aspartate aminotrasferase (AST) were r = 0.738/0.720 in CH-C and 0.506/0.515 in CH-B). 8-OHdG reactivity was strongly correlated with body and hepatic iron storage markers in CH-C (vs serum ferritin, r = 0.615; vs hepatic total iron score, r = 0.520; vs hepatic hepcidin mRNA levels, r = 0.571), although it was related to serum HBV-DNA titers (r = 0.540) and age of patients (r = -0.559) in CH-B. These results indicate that hepatic oxidative DNA damage is common in chronic viral hepatitis, in particular chronic HCV-infected patients, suggesting a possible link between chronic hepatic inflammation and hepatocarcinogenesis. The strong positive correlation between hepatic DNA damage and iron overload suggests that iron content is one of the most likely mediators of hepatic oxidative stress and iron reduction may be beneficial to reduce the incidence of hepatic cancer in CH-C patients.