Farinati F, Cardin R, De Maria N, Della Libera G, Marafin C, Lecis E, Burra P, Floreani A, Cecchetto A, Naccarato R
Cattedra Malattie Apparato Digerente, Università di Padova, Italy.
J Hepatol. 1995 Apr;22(4):449-56. doi: 10.1016/0168-8278(95)80108-1.
BACKGROUND/AIMS: Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation.
We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded.
Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.01 and 0.05); transferrin saturation is higher (p < 0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends.
These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.
背景/目的：关于丙型肝炎病毒相关肝损伤的发病机制，我们知之甚少。脂肪变性的存在或铁蛋白水平的升高，以及铁作为预后因素相关性的初步数据，促使我们确定丙型肝炎病毒相关肝损伤是否可能由铁蓄积介导。
我们评估了33例男性和20例女性慢性丙型肝炎病毒或乙型肝炎病毒相关肝炎患者（42 + 11）的肝脏炎症和脂肪变性程度、血清铁蛋白、转铁蛋白饱和度和铁水平、组织铁浓度和铁指数、肝脏谷胱甘肽和丙二醛。我们还纳入了6例同时有酒精滥用和丙型肝炎病毒感染的患者、4例男性慢性酒精性肝病患者和4例男性遗传性血色素沉着症患者，共67例。所有诊断均经组织学证实。排除肝硬化患者。
我们的数据显示：1. 脂肪变性在丙型肝炎病毒感染患者以及丙型肝炎病毒感染合并酒精滥用患者中更常见；2. 在男性中，丙型肝炎病毒感染阳性患者的血清铁蛋白和组织铁显著高于乙型肝炎病毒感染阳性患者（p < 0.01和0.05）；仅在综合考虑男性和女性时，丙型肝炎病毒感染阳性患者的转铁蛋白饱和度高于乙型肝炎病毒感染阳性患者（p < 0.05）；3. 血清铁蛋白和转铁蛋白饱和度仅与肝脏铁相关（r分别为0.833和0.695，p = 0.00001）；丙型肝炎病毒感染阳性患者的组织铁显著高于乙型肝炎病毒感染阳性患者（p < 0.05）；4. 在慢性肝炎患者中，血清铁蛋白在男性和女性中都是比转铁蛋白饱和度更好的肝脏铁储存标志物；5. 丙型肝炎病毒感染阳性患者丙二醛水平较高，谷胱甘肽周转活化，可能是对自由基介导的肝损伤的反应。女性肝脏铁水平较低，但趋势相似。
这些发现表明，丙型肝炎病毒相关肝损伤的特征是铁储存增加（可能由病毒诱导），这引发了自由基介导的过氧化反应，继而导致脂肪变性和谷胱甘肽周转活化。
