title: Cell death and nonalcoholic steatohepatitis: where is ballooning relevant?
abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the Western world. Progression to more aggressive forms of liver injury, such as nonalcoholic steatohepatitis (NASH) and cirrhosis, occurs in less than a third of affected subjects. Human data and both in vivo and in vitro models demonstrate that cell death, particularly apoptosis, is increased in NAFLD and NASH patients, suggesting that it is crucial in disease progression. Indeed, fatty acids - more specifically, saturated fatty acids - strongly induce hepatocyte apoptosis. In addition, hepatic steatosis renders hepatocytes more susceptible to apoptotic injury. Ballooned hepatocytes and Mallory-Denk bodies are important hallmarks of NASH and correlate with disease progression. There are complex correlations between ballooning, Mallory-Denk bodies and apoptosis through keratin metabolism and depletion, as well as through the endoplasmic reticulum stress response. Whether apoptosis may promote hepatocellular ballooning, or vice versa, will be discussed in this article.
authors.affiliation: Departamento de Gastrenterologia, Hospital Universitário de Santa Maria, Lisboa, Portugal.
authors.forename: Mariana Verdelho
authors.initials: MV
authors.lastname: Machado
authors.forename: Helena
authors.initials: H
authors.lastname: Cortez-Pinto
mesh_terms: D000818:Animals; D017209:Apoptosis; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease; D011506:Proteins / Q000378:metabolism
chemical_list: D005227:Fatty Acids; C027596:Mallory body protein, human; C488922:Mallory body protein, mouse; D011506:Proteins; D007633:Keratins