Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance
Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance
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DOI：
10.3748/wjg.v22.i1.72
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发表时间：
2016-01-07
影响因子：
4.3
通讯作者：
Geier, Andreas
中科院分区：
文献类型：
--
作者：
Dietrich, Christoph G.;Goetze, Oliver;Geier, Andreas
肝硬化是许多肝脏疾病的共同终点，并代表肝衰竭和肝细胞癌的相关风险。肝纤维化和肝硬化的进展伴随着肝功能的恶化。本文综述了I相和II相代谢酶以及转运蛋白的调节和功能变化，并提供了一个关于血脂和葡萄糖代谢的概述。有趣的是，I相酶通常在转录上下调，而II相酶大多在转录上保留，但其功能降低。转运蛋白以一种特定的方式进行调节，类似于在阻塞性胆汁淤积中观察到的分子变化。脂糖代谢以胰岛素抵抗和胰岛素抵抗为特征，导致能量消耗紊乱和浪费。可能的非侵入性测试，特别是呼吸测试，肝代谢的组成部分进行了讨论。肝脏代谢变化的异质性和复杂性使个体患者的肝功能评估复杂化。此外，在人类中进行的研究很少，物种差异排除了啮齿动物向人类转移数据的可能性。在临床实践中，一些已建立的全球评分或标准形成了肝硬化患者功能评估的基础，但困难的治疗决策，如选择移植或切除，需要进一步研究现有的非侵入性测试的应用和更具体的测试的发展。
Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.