McClain Craig J, Mokshagundam Sri Prakash L, Barve Shirish S, Song Zhenyuan, Hill Daniell B, Chen Theresa, Deaciuc Ion
Department of Internal Medicine, University of Louisville Medical Center, 530 South Jackson Street, ACB 3rd Floor, Louisville, KY 40292, USA.
Alcohol. 2004 Aug;34(1):67-79. doi: 10.1016/j.alcohol.2004.07.007.
In 1980, the term non-alcoholic steatohepatitis was coined to describe a new syndrome occurring in patients who usually were obese (often diabetic) females who had a liver biopsy picture consistent with alcoholic hepatitis, but who denied alcohol use. The causes of this syndrome were unknown, and there was no defined therapy. More than two decades later, this clinical syndrome is only somewhat better understood, and still there is no Food and Drug Administration-approved or even generally accepted drug therapy. Patients with primary non-alcoholic steatohepatitis typically have the insulin resistance syndrome (synonymous with the metabolic syndrome, syndrome X, and so forth), which is characterized by obesity, diabetes, hyperlipidemia, hypertension, and, in some instances, other metabolic abnormalities such as polycystic ovary disease. Secondary non-alcoholic steatohepatitis may be caused by drugs such as tamoxifen, certain industrial toxins, rapid weight loss, and so forth. The cause of non-alcoholic steatohepatitis remains elusive, but most investigators agree that a baseline of steatosis requires a second hit capable of inducing inflammation, fibrosis, or necrosis for non-alcoholic steatohepatitis to develop. Our research group has focused its efforts on the interactions of nutritional abnormalities, cytokines, oxidative stress with lipid peroxidation, and mitochondrial dysfunction in the induction of steatohepatitis, both alcoholic and non-alcoholic in origin. Research findings from other laboratories also support the role of increased cytokine activity, oxidative stress, and mitochondrial dysfunction in the pathogenesis of non-alcoholic steatohepatitis. The objectives of this article are to review the (1) definition and clinical features of non-alcoholic steatohepatitis, (2) potential mechanisms of non-alcoholic steatohepatitis, and (3) potential therapeutic interventions in non-alcoholic steatohepatitis.
1980年，“非酒精性脂肪性肝炎”一词被创造出来，用于描述一种出现在通常为肥胖（常伴有糖尿病）女性患者身上的新综合征。这些患者的肝脏活检图像与酒精性肝炎一致，但否认饮酒。该综合征的病因不明，也没有明确的治疗方法。二十多年后，对这种临床综合征的了解只是稍有增进，而且仍然没有获得美国食品药品监督管理局批准、甚至没有得到普遍认可的药物治疗方法。原发性非酒精性脂肪性肝炎患者通常患有胰岛素抵抗综合征（与代谢综合征、X综合征等同义），其特征为肥胖、糖尿病、高脂血症、高血压，在某些情况下还伴有其他代谢异常，如多囊卵巢综合征。继发性非酒精性脂肪性肝炎可能由他莫昔芬等药物、某些工业毒素、快速减肥等引起。非酒精性脂肪性肝炎的病因仍然不明，但大多数研究人员一致认为，脂肪变性的基线状态需要有第二次打击，能够诱发炎症、纤维化或坏死，非酒精性脂肪性肝炎才会发展。我们的研究小组一直致力于研究营养异常、细胞因子、氧化应激与脂质过氧化以及线粒体功能障碍之间的相互作用在酒精性和非酒精性脂肪性肝炎发病机制中的作用。其他实验室的研究结果也支持细胞因子活性增加、氧化应激和线粒体功能障碍在非酒精性脂肪性肝炎发病机制中的作用。本文的目的是综述：（1）非酒精性脂肪性肝炎的定义和临床特征；（2）非酒精性脂肪性肝炎的潜在发病机制；（3）非酒精性脂肪性肝炎的潜在治疗干预措施。
