[Etiopathogenesis of non-alcoholic steatohepatitis].
The <<double impact>> theory is the most widely accepted explanation for the pathogenesis of non-alcoholic steatohepatitis, while insulin resistance is a key factor. In the <<first impact>> the increased afflux of fatty acids to hepatocytes combined with decreased triglyceride elimination and lower fatty acid oxygenation leads to steatosis. The steatosis is not always quiescent, since the accumulated fatty acids are susceptible to a <<second impact>> in which the following factors intervene: a) oxidative stress with an increase in the production of oxygen free radicals which activate transcription factors such as NF-kappa, facilitating the formation of cytokines (tumor necrosis factor-alpha, tumor growth factor beta 1, interleukin-8 and Fas ligands; b) lipid peroxidation with the formation of malondialdehyde and 4-hydroxynonenal, promoting the afflux of inflammatory cells to the liver, depleting antioxidants such as glutathione, inducing the formation of Mallory bodies and increasing collagen synthesis on activating stellate cells, and c) leptin, endotoxins and iron overload, which together induce the lesions of steatohepatitis.
Pérez-Aguilar
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Servicio de Medicina Digestiva, Hospital La Fe, Valencia, España. fperezaguilar@terra.es
D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005609:Free Radicals; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism; D006946:Hyperinsulinism / Q000150:complications / Q000378:metabolism; D007249:Inflammation; D007333:Insulin Resistance; D019190:Iron Overload / Q000150:complications / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism
D016207:Cytokines; D005227:Fatty Acids; D005609:Free Radicals; D020738:Leptin; D009097:Multienzyme Complexes; D016328:NF-kappa B; D047492:Peroxisome Proliferator-Activated Receptors; D014280:Triglycerides; C526182:PRKAB1 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases