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September 8, 1975, Vol 233, No. 10 >
ARTICLE | September 8, 1975

Alcohol and Malnutrition in the Pathogenesis of Liver Disease FREE

Charles S. Lieber, MD
[+] Author Affiliations

Authorized for publication by the AMA Council on Foods and Nutrition, Philip L. White, ScD, Secretary.

Reprint requests to AMA Department of Foods and Nutrition, 535 N Dearborn St, Chicago, IL 60610.


JAMA. 1975;233(10):1077-1082. doi:10.1001/jama.1975.03260100047019
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References

Malnutrition is common among alcoholics because alcohol displaces protein-, vitamin-, and mineral-containing foods in the diet, and chronic alcohol consumption results in maldigestion and malabsorption of essential nutrients. In addition, alcohol exerts direct toxic effects on both the liver and gut, resulting in structural alterations in the intestine and the development of fatty liver, alcoholic hepatitis, and cirrhosis. Liver injury is preceded by an adaptive phase characterized by accelerated metabolism of drugs (including ethanol), and hyperlipemia, secondary to hypertrophy and hyperactivity of the smooth endoplasmic reticulum. Side effects include enhanced hepatotoxicity of CCI4 and possibly energy wastage. Alcoholics should not be led to believe that correction or prevention of nutritional deficiency will prevent liver damage in the face of continued alcohol abuse.

(JAMA 233:1077-1082, 1975)

REFERENCES

1 +
Baraona E, Pirola RC, Lieber CS:  Small intestinal damage and changes in cell population produced by ethanol ingestion in the rat . Gastroenterology 66:226-234, 1974;.
2 +
Lindenbaum J, Lieber CS:  Effects of chronic ethanol administration on intestinal absorption in man in the absence of nutritional deficiency . Ann NY Acad Sci , to be published.
3 +
Lindenbaum J, Lieber CS:  Hematologic effects of alcohol in man in the absence of nutritional deficiency . N Engl J Med 281:333-338, 1969;.
4 +
Rubin E, Lieber CS:  Alcohol-induced hepatic injury in nonalcoholic volunteers . N Engl J Med 278:869-876, 1968;.
5 +
Lieber CS, Jones DP, DeCarli LM:  Effects of prolonged ethanol intake: Production of fatty liver despite adequate diets . J Clin Invest 44:1009-1021, 1965;.
6 +
Lieber CS, DeCarli LM, Gang H, et al:  Hepatic effects of long-term ethanol consumption in primates , in Goldsmith El, Moor-Jankowski J (eds): Medical Primatology-1972 , Basel, Switzerland, S Karger, 1972;, pp 270-278.
7 +
Lieber CS, Spritz H, DeCarli LM:  Fatty liver produced by dietary deficiencies: Its pathogenesis and potentiation by ethanol . J Lipid Res 10:283-287, 1969;.
8 +
Moxley RT, Pozefsky T, Lockwood DH:  Protein nutrition and liver disease after jejunoileal bypass for morbid obesity . N Engl J Med 290:921-926, 1974;.
9 +
O'Leary JP, Maher JW, Hollenbeck JI, et al:  Pathogenesis of hepatic failure following jejunoileal bypass . Gastroenterology 66:859, 1974;.
10 +
Lieber CS, Spritz N:  Effects of prolonged ethanol intake in man: Role of dietary, adipose, and endogenously synthesized fatty acids in the pathogenesis of the alcoholic fatty liver . J Clin Invest 45:1400-1411, 1966;.
11 +
Lieber CS, Lefèvre A, Spritz N, et al:  Difference in hepatic metabolism of long- and medium-chain fatty acids: The role of fatty acid chain length in the production of the alcoholic fatty liver . J Clin Invest 46:1451-1460, 1967;.
12 +
Lieber CS, DeCarli LM:  An experimental model of alcohol feeding and liver injury in the baboon . J Med Primatol 3:153-163, 1974;.
13 +
Lieber CS, DeCarli LM:  Ethanol dependence and tolerance: A nutritionally controlled experimental model in the rat . Res Commun Chem Pathol Pharmacol 6:983-991, 1973;.
14 +
Lieber CS, Rubin E:  Alcoholic fatty liver in man on a high protein and low fat diet . Am J Med 44:200-206, 1968;.
15 +
Lieber CS:  Chronic alcoholic hepatic injury in experimental animals and man: Biochemical pathways and nutritional factors . Fed Proc 26:1443-1448, 1967;.
16 +
Lieber CS:  Hepatic and metabolic effects of alcohol (1966-1973) . Gastroenterology 65:821-846, 1973;.
17 +
Iseri OA, Lieber CS, Gottlieb LS:  The ultrastructure of fatty liver induced by prolonged ethanol ingestion . Am J Pathol 48:535-555, 1966;.
18 +
Lane BP, Lieber CS:  Ultrastructural alterations in human hepatocytes following ingestion of ethanol with adequate diets . Am J Pathol 49:593-603, 1966;.
19 +
Lefèvre A, Adler A, Lieber CS:  Effect of ethanol on ketone metabolism . J Clin Invest 49:1775-1782, 1970;.
20 +
Lieber CS, Jones DP, Losowsky MS, et al:  Interrelation of uric acid and ethanol metabolism in man . J Clin Invest 41:1863-1870, 1962;.
21 +
Korsten MA, Matsuzaki S, Feinman L, et al:  High blood acetaldehyde levels following ethanol administration: Difference between alcoholic and non-alcoholic subjects . N Engl J Med 292:386-389, 1975;.
22 +
Cederbaum AI, Lieber CS, Rubin E:  The effect of acetaldehyde on mitochondrial function . Arch Biochem Biophys 161:26-39, 1974;.
23 +
Ishii H, Joly J-G, Lieber CS:  Effect of ethanol on the amount and enzyme activities of hepatic rough and smooth microsomal membranes . Biochim Biophys Acta 291:411-420, 1973;.
24 +
Baraona E, Pirola RC, Lieber CS:  The pathogenesis of postprandial hyperlipemia in rats fed ethanol-containing diets . J Clin Invest 52:296-303, 1973;.
25 +
Teschke R, Hasumura Y, Lieber CS:  Hepatic microsomal ethanol oxidizing system, solubilization, isolation and characterization . Arch Biochem Biophys 163:404-415, 1974;.
26 +
Lieber CS, DeCarli LM:  Hepatic microsomal ethanol oxidizing system: In vitro characteristics and adaptive properties in vivo . J Biol Chem 245:2505-2512, 1970;.
27 +
Hasumura Y, Teschke R, Lieber CS:  Increased carbon tetrachloride hepatotoxicity, and its mechanism, after chronic ethanol consumption . Gastroenterology 66:415-422, 1974;.
28 +
Pirola RC, Lieber CS:  The energy cost of the metabolism of drugs, including ethanol . Pharmacology 7:185-196, 1972;.
29 +
Feinman L, Lieber CS:  Hepatic collagen metabolism: Effect of alcohol consumption in rats and baboons . Science 176:795, 1972;.
30 +
Lieber CS, DeCarli LM, Rubin E:  Sequential production of fatty liver, hepatitis and cirrhosis in sub-human primates fed ethanol with adequate diets . Proc Natl Acad Sci USA 72:437-441, 1975;.

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1 +
Baraona E, Pirola RC, Lieber CS:  Small intestinal damage and changes in cell population produced by ethanol ingestion in the rat . Gastroenterology 66:226-234, 1974;.
2 +
Lindenbaum J, Lieber CS:  Effects of chronic ethanol administration on intestinal absorption in man in the absence of nutritional deficiency . Ann NY Acad Sci , to be published.
3 +
Lindenbaum J, Lieber CS:  Hematologic effects of alcohol in man in the absence of nutritional deficiency . N Engl J Med 281:333-338, 1969;.
4 +
Rubin E, Lieber CS:  Alcohol-induced hepatic injury in nonalcoholic volunteers . N Engl J Med 278:869-876, 1968;.
5 +
Lieber CS, Jones DP, DeCarli LM:  Effects of prolonged ethanol intake: Production of fatty liver despite adequate diets . J Clin Invest 44:1009-1021, 1965;.
6 +
Lieber CS, DeCarli LM, Gang H, et al:  Hepatic effects of long-term ethanol consumption in primates , in Goldsmith El, Moor-Jankowski J (eds): Medical Primatology-1972 , Basel, Switzerland, S Karger, 1972;, pp 270-278.
7 +
Lieber CS, Spritz H, DeCarli LM:  Fatty liver produced by dietary deficiencies: Its pathogenesis and potentiation by ethanol . J Lipid Res 10:283-287, 1969;.
8 +
Moxley RT, Pozefsky T, Lockwood DH:  Protein nutrition and liver disease after jejunoileal bypass for morbid obesity . N Engl J Med 290:921-926, 1974;.
9 +
O'Leary JP, Maher JW, Hollenbeck JI, et al:  Pathogenesis of hepatic failure following jejunoileal bypass . Gastroenterology 66:859, 1974;.
10 +
Lieber CS, Spritz N:  Effects of prolonged ethanol intake in man: Role of dietary, adipose, and endogenously synthesized fatty acids in the pathogenesis of the alcoholic fatty liver . J Clin Invest 45:1400-1411, 1966;.
11 +
Lieber CS, Lefèvre A, Spritz N, et al:  Difference in hepatic metabolism of long- and medium-chain fatty acids: The role of fatty acid chain length in the production of the alcoholic fatty liver . J Clin Invest 46:1451-1460, 1967;.
12 +
Lieber CS, DeCarli LM:  An experimental model of alcohol feeding and liver injury in the baboon . J Med Primatol 3:153-163, 1974;.
13 +
Lieber CS, DeCarli LM:  Ethanol dependence and tolerance: A nutritionally controlled experimental model in the rat . Res Commun Chem Pathol Pharmacol 6:983-991, 1973;.
14 +
Lieber CS, Rubin E:  Alcoholic fatty liver in man on a high protein and low fat diet . Am J Med 44:200-206, 1968;.
15 +
Lieber CS:  Chronic alcoholic hepatic injury in experimental animals and man: Biochemical pathways and nutritional factors . Fed Proc 26:1443-1448, 1967;.
16 +
Lieber CS:  Hepatic and metabolic effects of alcohol (1966-1973) . Gastroenterology 65:821-846, 1973;.
17 +
Iseri OA, Lieber CS, Gottlieb LS:  The ultrastructure of fatty liver induced by prolonged ethanol ingestion . Am J Pathol 48:535-555, 1966;.
18 +
Lane BP, Lieber CS:  Ultrastructural alterations in human hepatocytes following ingestion of ethanol with adequate diets . Am J Pathol 49:593-603, 1966;.
19 +
Lefèvre A, Adler A, Lieber CS:  Effect of ethanol on ketone metabolism . J Clin Invest 49:1775-1782, 1970;.
20 +
Lieber CS, Jones DP, Losowsky MS, et al:  Interrelation of uric acid and ethanol metabolism in man . J Clin Invest 41:1863-1870, 1962;.
21 +
Korsten MA, Matsuzaki S, Feinman L, et al:  High blood acetaldehyde levels following ethanol administration: Difference between alcoholic and non-alcoholic subjects . N Engl J Med 292:386-389, 1975;.
22 +
Cederbaum AI, Lieber CS, Rubin E:  The effect of acetaldehyde on mitochondrial function . Arch Biochem Biophys 161:26-39, 1974;.
23 +
Ishii H, Joly J-G, Lieber CS:  Effect of ethanol on the amount and enzyme activities of hepatic rough and smooth microsomal membranes . Biochim Biophys Acta 291:411-420, 1973;.
24 +
Baraona E, Pirola RC, Lieber CS:  The pathogenesis of postprandial hyperlipemia in rats fed ethanol-containing diets . J Clin Invest 52:296-303, 1973;.
25 +
Teschke R, Hasumura Y, Lieber CS:  Hepatic microsomal ethanol oxidizing system, solubilization, isolation and characterization . Arch Biochem Biophys 163:404-415, 1974;.
26 +
Lieber CS, DeCarli LM:  Hepatic microsomal ethanol oxidizing system: In vitro characteristics and adaptive properties in vivo . J Biol Chem 245:2505-2512, 1970;.
27 +
Hasumura Y, Teschke R, Lieber CS:  Increased carbon tetrachloride hepatotoxicity, and its mechanism, after chronic ethanol consumption . Gastroenterology 66:415-422, 1974;.
28 +
Pirola RC, Lieber CS:  The energy cost of the metabolism of drugs, including ethanol . Pharmacology 7:185-196, 1972;.
29 +
Feinman L, Lieber CS:  Hepatic collagen metabolism: Effect of alcohol consumption in rats and baboons . Science 176:795, 1972;.
30 +
Lieber CS, DeCarli LM, Rubin E:  Sequential production of fatty liver, hepatitis and cirrhosis in sub-human primates fed ethanol with adequate diets . Proc Natl Acad Sci USA 72:437-441, 1975;.

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