Chow Monica D, Lee Yi-Horng, Guo Grace L
Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Division of Pediatric Surgery, Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Mol Aspects Med. 2017 Aug;56:34-44. doi: 10.1016/j.mam.2017.04.004. Epub 2017 May 5.
Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is marked by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear. However, multiple pathways have been proposed. A common link amongst many of these pathways is disruption of the homeostasis of bile acids. Other than aiding in the absorption of lipids and lipid-soluble vitamins, bile acids act as ligands. For example, they bind to farnesoid X receptor, which is critically involved in many of the pathways responsible for maintaining bile acid, glucose, and lipid homeostasis. Alterations to these pathways can lead to dysregulation of energy balance and increased inflammation and fibrosis. Repeated insults over time may be the key to development of steatohepatitis. For this reason, current drug therapies target aspects of these pathways to try to reduce and halt inflammation and fibrosis. This review will focus on the role of bile acids in these various pathways and how changes in these pathways may result in steatohepatitis. While there is no approved pharmaceutical treatment for either hepatic steatosis or steatohepatitis, this review will also touch upon the multitude of potential therapies.
非酒精性脂肪性肝病在全球的患病率正在上升。其特征是肝脏组织学上存在大泡性脂肪变，但临床上通常无症状。然而，它可进展为非酒精性脂肪性肝炎，这是一种更严重的肝病形式，其特征为炎症和纤维化。进一步发展会导致肝硬化，使患者易患肝细胞癌或肝衰竭。单纯性脂肪变进展为脂肪性肝炎的机制尚不完全清楚。然而，已经提出了多种途径。这些途径中的许多共同联系是胆汁酸稳态的破坏。除了有助于脂质和脂溶性维生素的吸收外，胆汁酸还作为配体。例如，它们与法尼醇X受体结合，该受体在许多负责维持胆汁酸、葡萄糖和脂质稳态的途径中起关键作用。这些途径的改变可导致能量平衡失调以及炎症和纤维化增加。随着时间的推移反复受到损伤可能是脂肪性肝炎发展的关键。因此，目前的药物治疗针对这些途径的各个方面，试图减轻和阻止炎症及纤维化。本综述将聚焦于胆汁酸在这些不同途径中的作用，以及这些途径的变化如何导致脂肪性肝炎。虽然目前尚无批准用于治疗肝脂肪变或脂肪性肝炎的药物，但本综述也将涉及众多潜在的治疗方法。
