Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C.
Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C.
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DOI：
10.1038/sj.bjc.6604204
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发表时间：
2008-02-12
影响因子：
8.8
通讯作者：
Takei, Y.
中科院分区：
文献类型：
--
作者：
Tanaka, H.;Fujita, N.;Sugimoto, R.;Urawa, N.;Horiike, S.;Kobayashi, Y.;Iwasa, M.;Ma, N.;Kawanishi, S.;Watanabe, S.;Kaito, M.;Takei, Y.
虽然氧化应激经常发生在慢性丙型肝炎患者中，但其在未来肝细胞癌（HCC）发展中的作用尚不清楚。使用1995年至2001年接受肝活检的118例初治患者的肝活检样本定量肝脏8-羟基脱氧鸟苷（8-OHdG）。评估8-OHdG对未来HCC发展的预测性及其与流行病学、生化和组织学基线特征的关系。在随访期间（平均6.7±3.3年），36例患者（30.5%）被确定为HCC。单因素分析显示，8-OHdG计数（65.2± 20.2vs40.0 ± 23.5cells/105 μm2，P<0.0001）等16个变量在HCC组与非HCC组间差异有统计学意义。考克斯比例风险分析显示，肝组织8-OHdG（P=0.0058）和肝纤维化（P=0.0181）是HCC的独立预测因素。值得注意的是，8-OHdG水平与身体和肝脏铁储存标志物正相关（相对于铁蛋白，P<0.0001，相对于肝脏铁评分，P<0.0001）。这项研究表明，氧化性DNA损伤与HCC风险增加相关，肝脏8-OHdG水平可作为识别极高风险亚组的标志物。肝DNA损伤与铁超载之间的强相关性表明，铁含量可能是氧化应激的强介质，铁减少可能降低慢性丙型肝炎患者的HCC发病率。
Although the oxidative stress frequently occurs in patients with chronic hepatitis C, its role in future hepatocellular carcinoma (HCC) development is unknown. Hepatic 8-hydroxydeoxyguanosine (8-OHdG) was quantified using liver biopsy samples from 118 naïve patients who underwent liver biopsy from 1995 to 2001. The predictability of 8-OHdG for future HCC development and its relations to epidemiologic, biochemical and histological baseline characteristics were evaluated. During the follow-up period (mean was 6.7±3.3 years), HCC was identified in 36 patients (30.5%). Univariate analysis revealed that 16 variables, including 8-OHdG counts (65.2±20.2 vs 40.0±23.5 cells per 105 μm2, P<0.0001), were significantly different between patients with and without HCC. Cox proportional hazard analysis showed that the hepatic 8-OHdG (P=0.0058) and fibrosis (P=0.0181) were independent predicting factors of HCC. Remarkably, 8-OHdG levels were positively correlated with body and hepatic iron storage markers (vs ferritin, P<0.0001 vs hepatic iron score, P<0.0001). This study showed that oxidative DNA damage is associated with increased risk for HCC and hepatic 8-OHdG levels are useful as markers to identify the extreme high-risk subgroup. The strong correlation between hepatic DNA damage and iron overload suggests that the iron content may be a strong mediator of oxidative stress and iron reduction may reduce HCC incidence in patients with chronic hepatitis C.
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影响因子：
9.8
作者：
El-Serag, HB;Richardson, PA;Everhart, JE
通讯作者：
Everhart, JE
DOI：
10.1073/pnas.81.13.4003
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
HOLLSTEIN, MC;BROOKS, P;AMES, BN
通讯作者：
AMES, BN
影响因子：
13.5
作者：
DESMET, VJ;GERBER, M;SCHEUER, PJ
通讯作者：
SCHEUER, PJ
影响因子：
13.5
作者：
Donato, F;Tagger, A;Nardi, G
通讯作者：
Nardi, G
DOI：
10.1111/j.1400-1746.2004.03549.x
发表时间：
2005-02-01
影响因子：
4.1
作者：
Silva, VSS;Perez, RM;Ferraz, MLG
通讯作者：
Ferraz, MLG