Nutritional and Metabolic Considerations in the Etiology of Nonalcoholic Steatohepatitis

The aim of this study was to determine if a relationship exists between nonalcoholic steatohepatitis (NASH) and serum levels of free fatty acids, choline deficiency, or celiac disease. Forty-seven patients with liver biopsy proven NASH were enrolled. Total serum free fatty acids and anti-endomysial antibodies were determined in all patients, while plasma free and phospholipid-bound choline were determined in 29 patients. Total serum free fatty acid concentration correlated significantly with female gender and serum albumin concentration. Patients with severe fibrosis on liver biopsy had significantly greater serum concentration of free fatty acids than patients without severe fibrosis. Plasma free and phospholipid-bound choline levels were normal and no significant correlation was found between the concentration of plasma free or phospholipid bound choline, and the severity of liver damage. Only one of the 47 patients with NASH had a positive titer for the anti-endomysial antibody. In conclusion, increased serum concentrations of free fatty acids were found in NASH and were associated with development of more severe liver disease. Neither choline deficiency nor celiac sprue by anti-endomysial antibody testing was associated with NASH.

[1]  D. Jenden,et al.  Choline deficiency: A cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation , 1995, Hepatology.

[2]  C. Trautwein,et al.  Stimulation of collagen α1(I) gene expression is associated with lipid peroxidation in hepatocellular injury: A link to tissue fibrosis? , 1994, Hepatology.

[3]  J. Partanen,et al.  Celiac disease risk in the USA: high prevalence of antiendomysium antibodies in healthy blood donors. , 1998, Scandinavian journal of gastroenterology.

[4]  K. Batts,et al.  Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis , 1999, Hepatology.

[5]  K. S. Lee,et al.  Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. , 1995, The Journal of clinical investigation.

[6]  K. Casper.  Plasma Choline Concentration in Humans Fed Parenterally NANCY F. SHEARD, JOHN A. TAYEK, BRUCE R. BISTRIAN, GEORGE L. BLACKBURN, AND STEVEN H. ZEISEL Am J Clin Nutr 43: 219-224, 1986 , 1986 .

[7]  B. Neuschwander‐Tetri,et al.  Original ContributionsNonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions , 1999 .

[8]  G. Blackburn,et al.  Plasma choline concentration in humans fed parenterally. , 1986, The American journal of clinical nutrition.

[9]  H. Bonkovsky,et al.  Management of Nonalcoholic Steatohepatitis: An Analytic Review , 2002, Journal of clinical gastroenterology.

[10]  R. Wiesner,et al.  Primary sclerosing cholangitis and celiac disease. A novel association. , 1988, Annals of internal medicine.

[11]  S. Mcmillan,et al.  Liver abnormalities associated with celiac sprue. How common are they, what is their significance, and what do we do about them? , 1995, Journal of clinical gastroenterology.

[12]  A. Axon,et al.  Acute fatty liver complicating coeliac disease , 1994 .

[13]  P. Baeuerle,et al.  Function and activation of NF-kappa B in the immune system. , 1994, Annual review of immunology.

[14]  R. Moxley,et al.  Protein nutrition and liver disease after jejunoileal bypass for morbid obesity. , 1974, The New England journal of medicine.

[15]  J. Olefsky,et al.  Effects of Weight Loss on Mechanisms of Hyperglycemia in Obese Non-Insulin-Dependent Diabetes Mellitus , 1986, Diabetes.

[16]  S. Zelman.  The liver in obesity. , 1952, A.M.A. archives of internal medicine.

[17]  K. Randig.  [DIABETES MELLITUS AND THE LIVER]. , 1965, Deutsches medizinisches Journal.

[18]  S. Zeisel.  Dietary choline: biochemistry, physiology, and pharmacology. , 1981, Annual review of nutrition.

[19]  D. Jenden,et al.  Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. , 1992, Gastroenterology.

[20]  K. Kawagoe,et al.  Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis. , 1987, The American journal of gastroenterology.

[21]  D. Jenden,et al.  Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. , 1992, Gastroenterology.

[22]  W. van Steenbergen,et al.  Liver disturbances in obesity and diabetes mellitus. , 1995, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[23]  N. Berg,et al.  HEPATIC INJURY IN ADULT CŒLIAC DISEASE , 1977, The Lancet.

[24]  R. Komorowski,et al.  Hepatic Free Fatty Acids in Alcoholic Liver Disease and Morbid Obesity , 2007, Hepatology.

[25]  D. Jenden,et al.  Low plasma free choline is prevalent in patients receiving long term parenteral nutrition and is associated with hepatic aminotransferase abnormalities. , 1993, Clinical nutrition.

[26]  C. Catassi,et al.  Coeliac disease in the year 2000: exploring the iceberg , 1994, The Lancet.

[27]  D. Jenden,et al.  Choline and phospholipid metabolism and the synthesis of acetylcholine in rat brain , 1979, Journal of neuroscience research.

[28]  M. Bardella,et al.  Prevalence of hypertransaminasemia in adult celiac patients and effect of gluten‐free diet , 1995, Hepatology.

[29]  E. Drenick,et al.  Hepatic steatosis after intestinal bypass--prevention and reversal by metronidazole, irrespective of protein-calorie malnutrition. , 1982, Gastroenterology.

[30]  D. Jenden,et al.  PLASMA CHOLINE: ITS TURNOVER AND EXCHANGE WITH BRAIN CHOLINE 1 , 1975, Journal of neurochemistry.

[31]  F. Schaffner,et al.  Fatty liver hepatitis and cirrhosis in obese patients. , 1979, The American journal of medicine.

[32]  BOULIN,et al.  Classification and Diagnosis of Diabetes. , 2022, Primary care.

[33]  B V Howard,et al.  Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects. , 1984, The Journal of clinical investigation.

[34]  W. Creutzfeldt,et al.  Liver diseases and diabetes mellitus. , 1970, Progress in liver diseases.

[35]  D. Pessayre,et al.  Acute and chronic hepatic steatosis lead to in vivo lipid peroxidation in mice. , 1996, Journal of hepatology.

[36]  G. Marinetti.  Disorders of Lipid Metabolism , 1990, Springer US.

[37]  R. Hanson,et al.  The natural history of nonalcoholic steatohepatitis: A follow‐up study of forty‐two patients for up to 21 years , 1990, Hepatology.

[38]  D. Jenden,et al.  Simultaneous measurement of endogenous and deuterium-labeled tracer variants of choline and acetylcholine in subpicomole quantities by gas chromatography-mass spectrometry. , 1973, Analytical biochemistry.

[39]  A. Peña Yáñez,et al.  [Disorders of lipid metabolism in uremia]. , 1978, Revista clinica espanola.

[40]  R. Haggitt,et al.  Pericentral hepatic fibrosis and intracellular hyalin in diabetes mellitus , 1980 .

[41]  C. Day,et al.  Steatohepatitis: a tale of two "hits"? , 1998, Gastroenterology.

[42]  G. Bray,et al.  Pathophysiology of obesity. , 1992, The American journal of clinical nutrition.

[43]  L. Terracciano,et al.  Elevated serum aminotransferase activity as an early manifestation of gluten-sensitive enteropathy. , 1993, The Journal of pediatrics.

[44]  D. Acosta,et al.  Injury produced by free fatty acids to lysosomes and mitochondria in cultured heart muscle and endothelial cells. , 1974, Atherosclerosis.

[45]  M. Clemens,et al.  Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[46]  D. Pessayre,et al.  Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. , 1998, Gastroenterology.

[47]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[48]  J. Murray.  Serodiagnosis of celiac disease. , 1997, Clinics in laboratory medicine.

[49]  K. Ishak,et al.  Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. , 1988, Gastroenterology.