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Iron metabolic disorder in chronic hepatitis C: Mechanisms and relevance to hepatocarcinogenesis

机译:慢性丙型肝炎中铁代谢紊乱的机制及其与肝癌发生的关系

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The liver is the major iron storage organ in the body, and therefore, iron metabolic disorder is sometimes involved in chronic liver diseases. Chronic hepatitis C is one of the liver diseases that show hepatic iron accumulation, even though its level should be recognized to be basically mild to moderate and sometimes within the normal range. The mechanisms underlying hepatic iron accumulation in chronic hepatitis C have not been fully elucidated. Reduction of the hepcidin transcription activity by hepatitis C virus (HCV)-induced reactive oxygen species may in part account for it, but the regulation of hepcidin is very complex and may depend on many variables, including the particular stage of the systemic and/or hepatic inflammatory conditions and the circulating transferrin-bound iron and intracellular iron stores. This might explain the variations in hepatic iron concentrations reported among patients with HCV-related chronic liver disease. However, even mild-to-moderate iron overload in the liver contributes to disease progression and hepatocarcinogenesis in chronic hepatitis C probably by reinforcing the HCV-induced oxidative stress through Fenton reaction. The present review highlights the current concept of hepatic iron overload status in chronic hepatitis C and discusses how iron metabolic disorder develops in this disease and the impact of hepatic iron overload on disease progression and its relevance to hepatocarcinogenesis.
机译:肝脏是人体中主要的铁存储器官,因此,铁代谢紊乱有时与慢性肝病有关。慢性丙型肝炎是显示肝铁蓄积的肝脏疾病之一,尽管应将其水平确定为轻度至中度,有时在正常范围内。慢性丙型肝炎中肝铁蓄积的机制尚未完全阐明。丙型肝炎病毒(HCV)诱导的活性氧对Hepcidin转录活性的降低可能是造成这种情况的部分原因,但是hepcidin的调节非常复杂,可能取决于许多变量,包括全身和/或肝炎性疾病以及与运铁蛋白结合的循环铁和细胞内铁的储存。这可能解释了HCV相关慢性肝病患者中报告的肝铁浓度变化。但是,即使肝脏中轻至中度的铁超载,也可能通过芬顿反应增强HCV诱导的氧化应激,从而导致慢性丙型肝炎的疾病进展和肝癌发生。本文概述了慢性丙型肝炎中肝铁超负荷状态的当前概念,并讨论了铁代谢紊乱如何在该疾病中发展以及肝铁超负荷对疾病进展的影响及其与肝癌发生的相关性。

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