Ответ: этиология цирроза
Background: Pathologic changes observed in patients with alcohol-induced liver disease can be divided into the following 3 groups: alcoholic fatty liver (simple steatosis), alcoholic hepatitis, and alcohol-related cirrhosis. Alcoholic fatty liver is an early and reversible consequence of excessive alcohol consumption.
Pathophysiology: The amount of fatty acid in the liver depends on the balance between the processes of delivery and removal. Fatty liver develops in every individual who consumes more than 60 g/d of alcohol. Many mechanisms of ethanol-induced fatty liver have been proposed. Increased hepatic levels of glycerol 3-phosphate (3-GP) following ethanol ingestion are related to an increase in the ratio of nicotinamide adenine dinucleotide, reduced form, (NADH) to nicotinamide adenine dinucleotide (NAD) in the liver. Increasing concentration of 3-GP results in enhanced esterification of fatty acids.
An increased level of free fatty acids also has been incriminated in the pathogenesis of fatty liver. Large amounts of alcohol enhance lipolysis because of direct stimulatory effect on the adrenal and pituitary axis. In addition, chronic ingestion of ethanol inhibits oxidation of fatty acids in the liver and release of very low-density lipoprotein (VLDL) into the blood. All of these mechanisms favor steatosis. Centrilobular localization of steatosis results from decreased energy stores from relative hypoxia and a shift in lipid metabolism, along with a shift in the redox reaction caused by the preferential oxidation of alcohol in the central zone.
Recent advancement in the understanding of the pathogenesis of alcoholic steatosis has provided some novel insights, including the role of peroxisome proliferator-activated receptor alpha, which is crucial for the regulation of hepatic fatty acid metabolism. Its blockade, in animal models, along with ethanol consumption, contributes to the development of alcoholic fatty liver. In addition, induction of adiponectin, a hormone secreted by adipocytes, has been implicated in the protective action of saturated fat against the development of alcoholic fatty liver in mice. Another recent finding is the role of early growth response-1 transcription factor (EGr-1), which is thought to be essential for ethanol-induced fatty liver injury in mice. Hepatocyte death by apoptosis occurs in the alcoholic fatty liver and has been demonstrated in rats and mice after ethanol feeding. This may be related to mitochondrial proteins that regulate apoptosis and necrosis and that are shown to be induced in mouse fatty liver models.
