Feldstein Ariel E, Gores Gregory J
Department of Pediatric Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH, USA.
Front Biosci. 2005 Sep 1;10:3093-9. doi: 10.2741/1765.
Alcohol liver disease (ALD) as well as nonalcoholic fatty liver disease (NAFLD) are two of the most common forms of chronic liver disease worldwide and may progress to cirrhosis and end stage liver disease. ALD and NAFLD seem to share many pathophysiologic mechanisms with the accumulation of lipids in the liver being the first step in the development of both conditions. While mitochondrial dysfunction and production of reactive oxygen species seem to play an important role in the progression from simple steatosis to steatohepatitis in both diseases, the pathogenesis of ALD and NAFLD as it relates to tissue injury remains poorly understood. Insights into these mechanisms are of significant clinical importance because current therapies for both conditions are limited and future therapies will be predicated by an understanding of their pathogenesis. In this review we focused on the current evidence for a central role of hepatocellular apoptosis, a specific form of cell death, in the pathogenesis of ALD and NAFLD as well as the current knowledge regarding the subcellular and molecular mechanisms involve in triggering hepatocyte apoptosis in these diseases.
酒精性肝病（ALD）和非酒精性脂肪性肝病（NAFLD）是全球最常见的两种慢性肝病形式，可能进展为肝硬化和终末期肝病。ALD和NAFLD似乎有许多共同的病理生理机制，肝脏中脂质的积累是这两种疾病发展的第一步。虽然线粒体功能障碍和活性氧的产生在这两种疾病从单纯性脂肪变性进展为脂肪性肝炎的过程中似乎起着重要作用，但ALD和NAFLD与组织损伤相关的发病机制仍知之甚少。深入了解这些机制具有重要的临床意义，因为目前针对这两种疾病的治疗方法有限，未来的治疗将取决于对其发病机制的理解。在这篇综述中，我们重点关注了肝细胞凋亡（一种特定形式的细胞死亡）在ALD和NAFLD发病机制中起核心作用的当前证据，以及目前关于这些疾病中触发肝细胞凋亡的亚细胞和分子机制的知识。
