Fatty liver alcoholism

Three liver disorders that are attributable to drinking are fatty liver, alcohol hepatitis, and cirrhosis. The first two disorders are reversible with abstinence cirrhosis, a leading killer in the United States, is not. 

Ethanol metabolism may result in alchohol-induced liver disease, including hepatic steatosis (fatty liver), alcohol-induced hepatitis, and cirrhosis. The principal toxic products of ethanol metabolism include acetaldehyde and free radicals. Acetaldehyde forms adducts with proteins and other compounds. The hydroxyethyl radical produced by MEOS and other radicals produced during... 

Alcohol-induced liver disease, a common and sometimes fatal consequence of chronic ethanol abuse, may manifest itself in three forms fatty liver, alcohol-induced hepatitis, and cirrhosis. Each may occur alone, or they may be present in any combination in a given patient. Alcohol-induced cirrhosis is discovered in up to 9% of all autopsies performed in the United States, with a peak incidence in patients 40 to 55 years of age. 

Rubin, E., and Lieber, C. S., 1974, Fatty liver, alcoholic hepatitis and cirrhosis produced by alcohol in primates, N. Engl. J. Med. 290 128. 

TOXICITY. No toxic effects have been observed. However, oral pharmacologic doses of up to 20 g per day of choline chloride used for periods of several weeks in the treatment of fatty liver, alcoholism, and kweishiorkor have caused some patients to experience dizziness, nausea, and diarrhea. 

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. 

Non-alcoholic fatty liver disease begins with asymptomatic fatty liver but may progress to cirrhosis. This is a disease of exclusion elimination of any possible viral, genetic, or environmental causes must be made prior to making this diagnosis. Non-alcoholic fatty liver disease is related to numerous metabolic abnormalities. Risk factors include diabetes mellitus, dyslipidemia, obesity, and other conditions associated with increased hepatic fat.26... 

In adults, a study of 75 autopsies of persons who had resided in a soft-water, leached soil region of North Carolina found a positive correlation between lead level in the aorta and death from heart-related disease (Voors et al. 1982). The association persisted after adjustment for the effect of age. A similar correlation was found between cadmium levels in the liver and death from heart-related disease. (Aortic lead and liver cadmium levels were considered to be suitable indices of exposure.) The effects of the two metals appeared to be additive. Potential confounding variables other than age were not included in the analysis. The investigators stated that fatty liver (indicative of alcohol consumption) and cigarette smoking did not account for the correlations between lead, cadmium and heart-disease death. 

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

There are many pathological effects of excessive alcohol consumption. The most important are neuronal and gonadal dysfunction, hypoglycaemia, fatty liver , and hepatitis, which can eventually lead to cirrhosis of the liver. 

Ethanol-related high levels of NADH+H and acetyl-CoA in the liver lead to increased synthesis of neutral fats and cholesterol. However, since the export of these in the form of VLDLs (see p. 278) is reduced due to alcohol, storage of lipids occurs (fatty liver). This increase in the fat content of the liver (from less than 5% to more than 50% of the dry weight) is initially reversible. However, in chronic alcoholism the hepatocytes are increasingly replaced by connective tissue. When liver cirrhosis occurs, the damage to the liver finally reaches an irreversible stage, characterized by progressive loss of liver functions. 

Hazle JD, Narayana PA, Dunsford HA. 1991. In wVoNMR, biochemical, and histologic evaluation of alcohol-induced fatty liver in rat and a comparison with CCh hepatotoxicity. Magn Reson Med 19 124-135. 

Athyros VG, Mikhailidis DP, Didangelos TP, Giouleme OI, Liberopoulos EN, Karagiannis A et al. Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome a randomised study. Cur Med Res Opin 2006 22(5) 873-83. 

Except for one case/° recent clinically oriented MRS studies of human liver have been at 1.5T. Several studies applied in vivo MRS to diffuse liver disease. ° °" The PDE intensity was lower in cirrhosis than in controls ° and served to distinguish the alcoholic, viral, and cholestatic etiologies of diffuse liver disease. ° However, there was no difference between patients with non-alcoholic fatty liver disease (NAFLD) and controls. Sharma et al., using the relative PME intensity as a measure of altered gluconeogenesis (this peak can contain glucose-6-P and 3-phos-phoglycerate in addition to PC and PE), found that hepatic gluconeogenesis was altered in both obese and non-obese Asian Indians with NAFLD, relative to non-obese subjects without NAFLD. 

Liver disease is the most common medical complication of alcohol abuse an estimated 15-30% of chronic heavy drinkers eventually develop severe liver disease. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the United States, chronic alcohol abuse is the leading cause of liver cirrhosis and of the need for liver transplantation. The risk of developing liver disease is related both to the average amount of daily consumption and to the duration of alcohol abuse. Women appear to be more susceptible to alcohol hepatotoxicity than men. Concurrent infection with hepatitis or C virus increases the risk of severe liver disease. 

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. 

This is the accumulation of triglycerides in hepatocytes, and there are a number of mechanisms underlying this response as is discussed below (see the sect. "Mechanisms of Toxicity"). The liver has an important role in lipid metabolism, and triglyceride synthesis occurs particularly in zone 3. Consequently, fatty liver is a common response to toxicity, often the result of interference with protein synthesis, and may be the only response as after exposure to hydrazine, ethionine, and tetracycline, or it may occur in combination with necrosis as with carbon tetrachloride. It is normally a reversible response, which does not usually lead to cell death, although it can be very serious as is the case with tetracycline-induced fatty liver in humans. Repeated exposure to compounds, which cause fatty liver, such as alcohol, may lead to cirrhosis. 

The use of metformin in patients with non-alcoholic fatty liver disease has been reported in two trials (123,124). Patients had abnormal liver function tests, which improved during the studies. No-one withdrew because of worsening of liver function tests or lactic acidosis. 

Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G. A randomised controlled trial of metformin versus vitamin E or prescriptive diet in non-alcoholic fatty liver disease. Am J Gastroenterol 2005 100 1082-90. 

Toxic effects to the liver are studied under the topic of hepatotoxicity, and substances that are toxic to the liver are called hepatotoxins. Much is known about hepatotoxicity from the many cases of liver toxicity that are a manifestation of chronic alcoholism.6 Liver injury from excessive alcohol ingestion initially hampers the ability of the organ to remove lipids, resulting in their accumulation in the liver (fatty liver). The liver eventually loses its ability to perform its metabolic functions and accumulates scar tissue, a condition known as cirrhosis. Inability to synthesize clotting factors can cause fatal hemorrhage in the liver. 

Hazle JD, Narayana PA, Dunsford HA (1991) In vivo NMR, biochemical, and histologic evaluation of alcohol-induced fatty liver in rat and a comparison with CC14 hepatotoxic-ity. Magnetic Resonance in Medicine 19 124-135 Hockings PD, Busza AL, Byrne J et al. (2003a) Validation of MRI measurement of cardiac output in the dog The effects of dobutamine and minoxidil. Toxicology Mechanisms Methods 13 39-43... 

Day, C. P., and Yeaman, S. J. The biochemistry of alcohol-induced fatty liver. Biochim. Biophys. Acta 1215, 33,1994. 

The increased levels of acetyl-CoA are diverted into fatty acid synthesis, and excess NADH promotes the synthesis of glycerol for fat synthesis this accounts for the fatty liver commonly found in alcoholics. Fatty acid oxidation is also suppressed. 

Non-alcoholic fatty liver disease (NAFID) and non-alcoholic steatohepatitis (NASH)... 

Liver disease is now recognised as a major complication of type 2 diabetes. Diabetes mellitus can lead to metabolic changes that alter normal hepatic and biliary function and structure. Type 2 diabetes is associated with an increased risk of a range of hepatobiliary diseases, including non-alcoholic fatty liver disease, cirrhosis, acute liver failure, hepatocellular carcinoma and cholelithiasis [22]. 

Anfossi G, Massucco P, Bonomo K, Trovati M (2004) Prescription of statins to dyslipidemic patients affected by liver diseases a subtle balance between risks and benefits. Nutr Metab Cardiovasc Dis 14 215-224. Gomez-Dominguez E, Gisbert J, Moreno-Monteagudo J, Garcia-Buey L, Moreno-Otero R (2006) A pilot study of atorvastatin treatment in dys-lipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 23 1643-1647. 

Liver damage from excessive ethanol consumption occurs in three stages. The first stage is the aforementioned development of fatty liver. In the second stage—alcoholic hepatitis—groups of cells die and inflammation results. This stage can itself be fatal. In stage three—cirrhosis—fibrous structure and scar tissue are produced around the dead cells. Cirrhosis impairs many of the liver s biochemical functions. The cirrhotic liver is unable to convert ammonia into urea, and blood levels of ammonia rise. Ammonia is toxic to the nervous system and can cause coma and death. Cirrhosis of the liver arises in about 25% of alcoholics, and about 75% of all cases of liver cirrhosis are the result of alcoholism. Viral hepatitis is a nonalcoholic cause of liver cirrhosis. 

Tang-B on, R, Vas, W., Weissman, J., Salimi, Z., Patel, R., Morris, L. Focal fatty liver lesions in alcoholic liver disease a broadened spectrum of CT appearances. Gastrointest. Radiol. 1985 10 133—137... 

Alcohol With regard to hepatotoxins, by far the greatest importance must be attributed to alcohol. The development of alcohol-mediated portal hypertension is complex. The increasing accumulation of fat in the hepatic cells interferes with the microcirculation, since the sinusoids become both longer and narrower as a result of fatty degeneration of the hepatocytes. In cases of fatty liver, a greater microcirculation is observed in the arterioles at the same time. Stimulation of the Ito cells is an important pathogenic... 

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