Metabolic alterations and hepatitis C: From bench to bedside
Metabolic alterations and hepatitis C: From bench to bedside
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DOI：
10.3748/wjg.v22.i4.1461
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发表时间：
2016-01-28
影响因子：
4.3
通讯作者：
Chang, Ming-Ling
中科院分区：
文献类型：
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作者：
Chang, Ming-Ling
除了引起肝硬化和肝细胞癌之外，丙型肝炎病毒（HCV）被认为引起低脂血症、肝脂肪变性、胰岛素抵抗、代谢综合征和糖尿病。丙型肝炎病毒的病毒生命周期取决于宿主细胞中的胆固醇代谢。HCV核心蛋白和非结构蛋白5A干扰B关键的脂质和葡萄糖途径，如固醇调节元件结合蛋白途径和蛋白激酶B/哺乳动物雷帕霉素靶蛋白/S6激酶1途径。尽管几种表达核心或完整HCV蛋白的转基因小鼠表现出肝脂肪变性和/或血脂异常，但它们是否完全反映了HCV感染人类的代谢改变仍不清楚。许多横断面研究表明，慢性丙型肝炎（CHC）患者的代谢改变和心血管事件的患病率增加;然而，存在相互矛盾的结果，主要是由于不可避免的个体差异。利用抗HCV治疗，大多数慢性丙型肝炎患者的纵向队列研究已经证明了病毒清除在减轻代谢改变和心血管风险方面的有利作用。为了确定慢性丙型肝炎患者HCV相关代谢改变和相关并发症的风险，有必要在抗HCV治疗后进行长期随访，以调整关键的混杂因素，如HCV基因型和宿主基线葡萄糖代谢。脂肪组织是一种重要的内分泌器官，其分泌的脂肪细胞因子可调节糖、脂代谢。然而，大多数关于HCV感染和脂肪细胞因子改变的数据是不确定的。一个全面的概述丙型肝炎相关的代谢和脂肪细胞因子的改变，从板凳到床边，提出了这个主题的亮点。
In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C (CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight.