Apoptosis in alcoholic and nonalcoholic steatohepatitis.
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.
Feldstein
Ariel E
AE
Department of Pediatric Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH, USA.
Gores
Gregory J
GJ
D000818:Animals; D017209:Apoptosis; D018450:Disease Progression; D005234:Fatty Liver / Q000473:pathology*; D005235:Fatty Liver, Alcoholic / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans