Lalor Patricia F, Faint Jeff, Aarbodem York, Hubscher Stefan G, Adams David H
Liver Research Group, MRC Centre for Immune Regulation, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham, United Kingdom.
Semin Liver Dis. 2007 May;27(2):173-93. doi: 10.1055/s-2007-979470.
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) share similar morphological characteristics despite the obvious etiological differences between the two conditions. In both conditions the first manifestation of injury is the accumulation of fat within hepatocytes (steatosis), and in a proportion of patients this is followed by the development of necroinflammatory activity that leads to cirrhosis. Steatosis alone is considered to be relatively innocuous and is usually reversible, and it is the development of liver cell ballooning and inflammation (steatohepatitis) that determines whether a patient progresses to irreversible liver damage and fibrosis. This has led to the two-hit theory in which the first hit is accumulation of fat in the liver and the second hit involves an inflammatory insult or challenge to the liver, for example, through oxidative stress or in response to pathogenic stimuli such as endotoxin. Although the nature of the hits remains poorly understood, it is clear that the critical event in progression is the development of inflammation, and the fact that it is impossible to distinguish alcoholic from nonalcoholic steatohepatitis on histological grounds suggests that common pathogenic mechanisms are involved. We focus on the role of cytokines and particularly chemokines in instigating and driving the inflammatory infiltrate in steatohepatitis. A better understanding of this process might allow therapeutic intervention to switch off the inflammatory response before irreversible damage occurs in both ALD and NAFLD.
非酒精性脂肪性肝病（NAFLD）和酒精性肝病（ALD）尽管病因明显不同，但具有相似的形态学特征。在这两种疾病中，损伤的最初表现都是肝细胞内脂肪堆积（脂肪变性），并且在一部分患者中，随后会发展为坏死性炎症活动，进而导致肝硬化。单纯的脂肪变性被认为相对无害且通常是可逆的，而肝细胞气球样变和炎症（脂肪性肝炎）的发展才决定患者是否会进展为不可逆的肝损伤和纤维化。这导致了“二次打击”学说，其中第一次打击是肝脏中脂肪的堆积，第二次打击涉及对肝脏的炎症性损伤或挑战，例如通过氧化应激或对内毒素等致病刺激的反应。尽管对这些打击的本质仍了解甚少，但很明显疾病进展中的关键事件是炎症的发展，而且基于组织学无法区分酒精性和非酒精性脂肪性肝炎这一事实表明，其中涉及共同的致病机制。我们重点关注细胞因子尤其是趋化因子在引发和推动脂肪性肝炎炎症浸润中的作用。更好地理解这一过程可能会使治疗干预能够在ALD和NAFLD发生不可逆损伤之前抑制炎症反应。
