Aoki Christopher A, Rossaro Lorenzo, Ramsamooj Rajendra, Brandhagen David, Burritt Mary F, Bowlus Christopher L
Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA.
J Clin Gastroenterol. 2005 Jan;39(1):71-4.
Liver iron is frequently elevated in chronic hepatitis C and may contribute to liver injury. The pathophysiology behind this phenomenon may involve hepcidin, a gene that is up-regulated in the liver by inflammation and iron. Inappropriately low hepcidin is important to the pathophysiology of hereditary hemochromatosis. However, the role of hepcidin in the iron loading of patients with hepatitis C is unknown.
To determine whether liver hepcidin mRNA correlates with markers of hepatic inflammation and iron status in patients with hepatitis C, we extracted total RNA from liver biopsy specimens of patients with chronic hepatitis C and quantified hepcidin mRNA. Liver hepcidin mRNA levels were then correlated with aspartate aminotransferase, alanine aminotransferase, ferritin, viral load, fibrosis, hepatic iron concentration, and Hepatic Activity Index (HAI).
Among patients with hepatitis C, there was a significant correlation of hepcidin mRNA expression in the liver with hepatic iron concentration and serum ferritin (r = 0.72, P = 0.006, and r = 0.60, P = 0.01, respectively). Hepcidin mRNA expression in the liver did not correlate with aspartate aminotransferase, alanine aminotransferase, HAI, or viral load. No differences in hepcidin mRNA were found based on viral genotype or the presence of fibrosis.
In contrast to other inflammatory states, hepcidin mRNA expression in the liver was independent of markers of inflammation in hepatitis C. Instead, our results suggest that iron stores in patients with hepatitis C regulate hepcidin expression and that iron loading in chronic hepatitis C is not due to inappropriate hepcidin expression.
慢性丙型肝炎患者肝脏铁含量常升高，可能导致肝损伤。这种现象背后的病理生理学机制可能涉及铁调素，该基因在肝脏中会因炎症和铁而被上调。铁调素水平异常低下对遗传性血色素沉着症的病理生理学很重要。然而，铁调素在丙型肝炎患者铁负荷中的作用尚不清楚。
为了确定肝脏铁调素mRNA是否与丙型肝炎患者的肝脏炎症和铁状态标志物相关，我们从慢性丙型肝炎患者的肝活检标本中提取了总RNA，并对铁调素mRNA进行了定量分析。然后将肝脏铁调素mRNA水平与天冬氨酸转氨酶、丙氨酸转氨酶、铁蛋白、病毒载量、纤维化、肝脏铁浓度和肝脏活动指数（HAI）进行相关性分析。
在丙型肝炎患者中，肝脏中铁调素mRNA表达与肝脏铁浓度和血清铁蛋白显著相关（分别为r = 0.72，P = 0.006，以及r = 0.60，P = 0.01）。肝脏中铁调素mRNA表达与天冬氨酸转氨酶、丙氨酸转氨酶、HAI或病毒载量无关。基于病毒基因型或纤维化的存在，未发现铁调素mRNA有差异。
与其他炎症状态不同，丙型肝炎患者肝脏中铁调素mRNA表达与炎症标志物无关。相反，我们的结果表明，丙型肝炎患者的铁储存调节铁调素表达，且慢性丙型肝炎的铁负荷并非由于铁调素表达不当所致。
