Liver diseases represent a critical health problem with 2 million deaths worldwide per year, mainly due to cirrhosis and its complications. Oxidative stress plays an important role in the development of liver diseases. In order to maintain an adequate homeostasis, there must be a balance between free radicals and antioxidant mediators. Nuclear factor erythroid 2-related factor (Nrf2) and its negative regulator Kelch-like ECH-associated protein 1 (Keap1) comprise a defense mechanism against oxidative stress damage, and growing evidence considers this signaling pathway as a key pharmacological target for the treatment of liver diseases. In this review, we provide detailed and updated evidence regarding Nrf2 and its involvement in the development of the main liver diseases such as alcoholic liver damage, viral hepatitis, steatosis, steatohepatitis, cholestatic damage, and liver cancer. The molecular and cellular mechanisms of Nrf2 cellular signaling are elaborated, along with key and relevant antioxidant drugs, and mechanisms on how Keap1/Nrf2 modulation can positively affect the therapeutic response are described. Finally, exciting recent findings about epigenetic modifications and their link with regulation of Keap1/Nrf2 signaling are outlined.

中文翻译：

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Nrf2在肝病中的作用：分子，药理和表观遗传方面。

肝病是一个至关重要的健康问题，全世界每年主要由于肝硬化及其并发症导致200万人死亡。氧化应激在肝病的发展中起重要作用。为了维持足够的动态平衡，自由基和抗氧化剂介体之间必须保持平衡。核因子类胡萝卜素2相关因子（Nrf2）及其负调节剂Kelch样ECH相关蛋白1（Keap1）构成了抗氧化应激损伤的防御机制，越来越多的证据认为该信号通路是治疗甲氧西林的关键药理靶标肝脏疾病。在这篇评论中，我们提供有关Nrf2及其与主要肝脏疾病（如酒精性肝损害，病毒性肝炎，脂肪变性，脂肪性肝炎，胆汁淤积损害和肝癌。详细阐述了Nrf2细胞信号传导的分子和细胞机制，以及关键和相关的抗氧化剂药物，并描述了Keap1 / Nrf2调控如何积极影响治疗反应的机制。最后，概述了有关表观遗传修饰及其与Keap1 / Nrf2信号调节的联系的令人兴奋的最新发现。