The Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Department of Endoscopy and Ultrasound, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Int J Mol Med. 2017 Aug;40(2):263-270. doi: 10.3892/ijmm.2017.3015. Epub 2017 Jun 9.
Excessive alcohol consumption is the most common cause of liver disease in the world. Chronic alcohol abuse leads to liver damage, liver inflammation, fibrosis and hepatocellular carcinoma. Inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, induce liver injury, which leads to the develo-pment of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as interleukin (IL)-6 and IL-10, are also associated with ALD. IL-6 improves ALD via the activation of STAT3 and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. Alcohol consumption promotes liver inflammation by incre-asing the translocation of gut-derived endotoxins to the portal circulation and by activating Kupffer cells through the lipopolysaccharide/Toll-like receptor 4 pathways. Oxidative stress and microflora products are also associated with ALD. Hepatic stellate cells play an important role in angiogenesis and liver fibrosis. Anti-angiogenic therapy has been found to be effective in the prevention of fibrosis. This suggests that blocking angiogenesis could be a promising therapeutic option for patients with advanced fibrosis. This review discusses the main pathways associated with liver inflammation and liver fibrosis as well as new therapeutic strategies.
过量饮酒是世界范围内导致肝脏疾病的最常见原因。慢性酒精滥用会导致肝脏损伤、肝脏炎症、纤维化和肝细胞癌。炎症细胞因子,如肿瘤坏死因子-α和干扰素-γ,会诱导肝损伤,从而导致酒精性肝病(ALD)的发生。抗炎细胞因子,如白细胞介素(IL)-6 和 IL-10,也与 ALD 相关。IL-6 通过激活 STAT3 并随后诱导肝细胞中多种肝保护基因的表达来改善 ALD。饮酒通过增加肠道来源的内毒素向门静脉循环的易位,并通过脂多糖/Toll 样受体 4 途径激活枯否细胞来促进肝脏炎症。氧化应激和微生物群落产物也与 ALD 相关。肝星状细胞在血管生成和肝纤维化中发挥重要作用。抗血管生成治疗已被发现可有效预防纤维化。这表明阻断血管生成可能是治疗晚期纤维化患者的一种有前途的治疗选择。本综述讨论了与肝脏炎症和肝纤维化相关的主要途径以及新的治疗策略。