Moderate Drinking, Inflammation, and Liver Disease
Introduction
Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. Alcohol-induced reactive oxygen and nitrogen species, as well as inflammatory and genetic factors, contribute to the development and progression of ALD. In contrast to the effects on coronary heart disease, moderate alcohol consumption has no benefit for liver disease and may even cause liver disease in susceptible individuals. Activation of inflammatory pathways by long-term heavy alcohol intake, as opposed to attenuation of inflammation by acute moderate alcohol consumption, likely contributes to some of the organ-specific effects of alcohol.
Section snippets
Alcohol Consumption and Liver Disease
While multiple studies suggest a beneficial effect of moderate alcohol consumption on coronary heart disease, a linear correlation exists between the amount and duration of alcohol use and liver disease. In the Western world, up to 50% of cases of end-stage liver disease are related to alcohol use (1). The “threshold” of alcohol consumption associated with ALD depends on the daily amount and the duration of alcohol intake. Furthermore, gender difference is a major factor in ALD. In males, a
Mechanisms of Liver Injury and the Role of Inflammation in Alcoholic Liver Disease
The mechanisms by which alcohol consumption causes liver damage involves a number of physiological and biochemical changes that lead to liver pathology. Alcohol dehydrogenase (ADH) is the dominant enzyme in alcohol oxidation producing acetaldehyde, which is further oxidized to acetate by aldehyde dehydrogenase (ALDH). When tissue alcohol levels exceed 10 mmol/L concentration, the microsomal enzyme cytochrome P450 2E1 (Cyp2E) is induced and participates in alcohol metabolism. It has been
Different Regulation of Inflammatory Pathways by Acute and Chronic Alcohol Use
Increasing evidence suggests that in contrast to the proinflammatory activation in alcoholic hepatitis by chronic excessive alcohol consumption, acute alcohol administration has anti-inflammatory effects. Consistent with this notion, peripheral blood monocytes obtained from patients with alcoholic hepatitis spontaneously produced increased amounts of TNFα and responded to ex vivo LPS stimulation with increased TNFα levels 19, 28, while acute alcohol consumption in normal volunteers results in
Conclusions
Moderate alcohol use in the amount of 20 to 30 g/d for men and 10 to 15 g for women is likely to be safe for most individuals. Nevertheless, an individual's threshold for alcohol-induced liver disease depends on multiple susceptibility factors and coexisting liver conditions. The presumed “safe” limits of alcohol use, therefore, cannot apply to people with cofactors such as chronic viral hepatitis, obesity, hemochromatosis, and other factors that increase the susceptibility of the liver to
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