Alcoholism liver disease

Ethanol also inhibits ADH-catalyzed retinol oxidation in vitro, and ethanol treatment of mouse embtyos has been demonstrated to reduce endogenous RA levels. The inhibition of cytosolic RolDH activity and stimulation of microsomal RolDH activity could explain ethanol-mediated vitamin A depletion, separate from ADH isoenzymes. Although the exact mechanism of inhibition of retinoid metabolism by ethanol is unclear, these observations are consistent with the finding that patients with alcoholic liver disease have depletedhepatic vitamin A reserves [review see [2]. 

There are no studies in humans directly demonstrating increased production of ROM in alcoholic liver disease. However, indirect evidence does support the hypothesis that ROM are involved in the pathogenesis of ethanolic liver injury (Arthur, 1988 Tsukamoto et al., 1990 Nordmann et /., 1992). Basal whole blood... 

Allopurinol has been shown to attenuate lipid peroxidation in ethanol-fed rats (Kato etal., 1990). However, this was not correlated with any possible effect on histological damage and, as discussed previously, the significance of lipid peroxidation is unclear. Despite the evidence suggesting that oxidative stress and increased oxidative metabolism may play a role in the pathogenesis of human alcoholic liver disease, it remains to be shown that treatment with specific antioxidants will modify this process. 

Whilst there is some evidence that ethanol can induce increased production of ROM and that ischaemia may be involved in the pathogenesis of alcoholic liver disease, there is very little data to show that specific antioxidants can modify the disease process. 

Gerli, G., Locatelli, G.F., Mongiat, R., Zenoni, L., Agostoni, A., Moschini, G., Zafiropoulos, D., Bruno, S., Rossi, S., Vignati, A. Tarolo, G. and Podda, M. (1992). Erythrocyte antioxidant activity, serum caeruloplasmin, and trace element levels in subjects with alcoholic liver disease. Am. J. Clin. Pathol. 97, 614-618. 

Kamimura, S., Gaal, K., Britton, R.S., Bacon, B.R., Triadafilopoulos, G. and Tsukamoto, H. (1992). Increased 4-hydroxynonenal levels in experimental alcoholic liver disease association of lipid peroxidation with liver fibrogenesis. Hepatology 16, 448-453. 

Shaw, S., Rubin, K.P. and Lieber, C.S. (1983). Depressed hepatic glutathione and increased diene conjugation in alcoholic liver disease. Dig. Dis. Sci. 28, 585-587. 

Suematsu, T., Matsumura, T. and Sato, N. (1981). Lipid peroxidation in alcoholic liver disease in humans. Alcoholism Clin. Exp. Res. 5, 427-30. 

Cirrhosis is the result of long-term insult to the liver, so damage is typically not evident clinically until the fourth decade of life. Chronic liver disease and cirrhosis combined were the 12th leading cause of death in the United States in 2002. In patients between the ages of 25 and 64, damage from excessive alcohol use accounted for over one-half of the deaths.2 Alcoholic liver disease and viral hepatitis are the most common causes of cirrhosis in the United States and worldwide. 

Progression of alcoholic liver disease moves through several distinct phases from development of fatty liver to the development of alcoholic hepatitis and cirrhosis. Fatty liver and alcoholic hepatitis may be reversible with cessation of alcohol intake, but cirrhosis itself is irreversible. Although the scarring of cirrhosis is permanent, maintaining abstinence from alcohol can still decrease complications and slow development to end-stage liver disease.22 Continuing to imbibe speeds the advancement of liver dysfunction and its complications. 

Lifestyle modifications can limit disease complications and slow further liver damage. Avoidance of additional hepatic insult is critical for successful cirrhosis treatment. The only proven treatment for alcoholic liver disease is the immediate cessation of alcohol consumption. Patients who have cirrhosis from etiologies other than alcoholic liver disease should also abstain from alcohol consumption to prevent further liver damage. 

Shiraishi K, Matsuzaki S, Ishida H, Nakazawa H (1993) Impaired erythrocyte deformability and membrane fluidity in alcoholic liver disease participation in disturbed hepatic microcirculation. Alcohol Alcohol Suppl lA 59-64... 

Whitfield JB. Meta-analysis of the effects of alcohol dependence and alcoholic liver disease. Alcohol Alcohol 1997 32 613-619. 

Absolute contraindications to warfarin include active bleeding, hemorrhagic tendencies, pregnancy, and a history of warfarin-induced skin necrosis. It should be used with great caution in patients with a history of GI bleeding, recent neurosurgery, alcoholic liver disease, severe renal... 

Takamatsu, M. et al., Genetic polymorphisms of interleukin-1 beta in association with the development of alcoholic liver disease in Japanese patients, Am. J. Gastroenterol., 95 (5), 1305, 2000. 

Accumulation of cytoplasmic NADH and glycerol 3-P may also contribute to lipid accumulation in alcoholic liver disease. Free fatty acids released from adipose in part enter the liver where P-oxidation is very slow (high NADH). In the presence of high glycerol-3P, fatty acids are inappropriately stored in the liver as triglyceride. 

Alcoholic liver disease, AST increases more than ALT... 

The main indications for liver transplantation include chronic hepatitis C, alcoholic liver disease, nonalcoholic fatty liver disease, and cryptogenic cirrhosis. 

Patients with psoriasis or RA who have any of the following alcoholism, alcoholic liver disease, or other chronic liver disease overt or laboratory evidence of immunodeficiency syndromes preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia). 

The main acute effect is inebriation, which in turn spawns violence, spousal and child abuse, crime, motor vehicle accidents, workplace and home accidents, drowning, suicide, and accidental death. The chronic effects include alcoholism, liver disease, various forms of cancer, brain disorders, cardiovascular disease and other organ system effects, absence from or loss of work, family dysfunction, and malnutrition. 

Contraindications Active alcoholism, liver disease, or viral hepatitis, all of which increase the risk of hepaf ofoxicity... 

Hunt, N. C. A., and Goldin, R. D. (1992). Nitric oxide production by monocytes in alcoholic liver disease. J. Hepatol. 14, 146-150. 

The pathogenesis of alcoholic liver disease is a multifactorial process involving metabolic repercussions of ethanol oxidation in the liver, dysregulation of fatty acid oxidation and synthesis, and activation of the innate immune system by a combination of direct effects of ethanol and its metabolites and by bacterial endotoxins that access the liver as a result of ethanol-induced changes in the intestinal tract. Tumor necrosis factor- , a proinflammatory cytokine that is consistently... 

You M, Crabb DW Recent advances in alcoholic liver disease II. Minireview Molecular mechanisms of alcoholic fatty liver. Am J Physiol Gastrointest Liver Physiol 2004 287 G1. 

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