Advertisement

Nonalcoholic Fatty Liver Disease and Steatohepatitis

  • Erin M. McCarthy
  • Mary E. RinellaEmail author
Chapter

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world. NAFLD is tightly linked to insulin resistance and considered to be the hepatic manifestation of the metabolic syndrome. Obesity is a well-documented risk factor for NAFLD. The cornerstone of any treatment regimen for patients with NAFLD is lifestyle modification focused on weight loss, exercise, and improvements in insulin sensitivity. Sustained and gradual weight loss is the most effective treatment for NAFLD. The roles of diet, nutrient composition, and physical activity in the management of NAFLD are outlined in this chapter.

Keywords

Lifestyle Nutrition Obesity NAFLD NASH Fatty liver Weight loss 

Abbreviations

AA

Arachidonic acid

ACSM

American College of Sports Medicine

AGB

Adjustable gastric band

ALA

α-linolenic acid

ALB

Albumin

ALKPHOS

Alkaline phosphatase

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

BMI

Body Mass Index

CAD

Coronary artery disease

CBT

Cognitive behavioral therapy

CHD

Coronary heart disease

CHO

Carbohydrates

CVD

Cardiovascular disease

DHA

Docosahexaenoic acid

DNL

De novo lipogenesis

EPA

Eicosapentaenoic acid

FA

Fatty acid

GI

Gastrointestinal

HCC

Hepatocellular carcinoma

HDL

High-density lipoprotein

HFCS

High-fructose corn syrup

IL-6

Interleukin-6

IHS

Isolated hepatic steatosis

LA

Linoleic acid

LDL-cholesterol

Low-density lipoprotein cholesterol

MUFA

Monounsaturated fatty acid

NAFLD

Nonalcoholic Fatty Liver Disease

NASH

Nonalcoholic steatohepatitis

NHANES

National Health and Nutrition Examination Survey

PUFA

Polyunsaturated fatty acid

RYGB

Roux-en-y gastric bypass

SFAs

Saturated fatty acids

TBILI

Total bilirubin

TGs

Triglycerides

TNF-α

Tumor necrosis factor alpha

VAT

Visceral adipose tissue

VLDL

Very low-density lipoprotein

VSG

Vertical sleeve gastrectomy

WHO

World Health Organization

References

  1. 1.
    Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol. 2005;42(1):132–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Trivedi IR. ME NAFLD and Cardiovascular Disease: Can the Real Association Be Determined? Curr Hepatol Rep 2014. 2014.Google Scholar
  3. 3.
    Capristo E, Miele L, Forgione A, et al. Nutritional aspects in patients with non-alcoholic steatohepatitis (NASH). Eur Rev Med Pharmacol Sci. 2005;9(5):265–8.PubMedGoogle Scholar
  4. 4.
    Centis E, Marzocchi R, Suppini A, et al. The role of lifestyle change in the prevention and treatment of NAFLD. Curr Pharm Des. 2013;19(29):5270–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Kim NH, Kim JH, Kim YJ, et al. Clinical and metabolic factors associated with development and regression of nonalcoholic fatty liver disease in nonobese subjects. Liver Int. 2014;34:604–11.CrossRefPubMedGoogle Scholar
  6. 6.
    Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387–95.CrossRefPubMedGoogle Scholar
  7. 7.
    Consultation WHOE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157–63.CrossRefGoogle Scholar
  8. 8.
    Chitturi S, Wong VW, Farrell G. Nonalcoholic fatty liver in Asia: firmly entrenched and rapidly gaining ground. J Gastroenterol Hepatol. 2011;26(Suppl 1):163–172.CrossRefPubMedGoogle Scholar
  9. 9.
    Fan JG, Zhu J, Li XJ, et al. Fatty liver and the metabolic syndrome among Shanghai adults. J Gastroenterol Hepatol. 2005;20(12):1825–1832.CrossRefPubMedGoogle Scholar
  10. 10.
    Park SH, Jeon WK, Kim SH, et al. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol. 2006;21(1 Pt 1):138–143.CrossRefPubMedGoogle Scholar
  11. 11.
    Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, et al. Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology. 2008;48(6):1791–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Booth FW, Laye MJ, Lees SJ, Rector RS, Thyfault JP. Reduced physical activity and risk of chronic disease: the biology behind the consequences. Eur J Appl Physiol. 2008;102(4):381–390.CrossRefPubMedGoogle Scholar
  13. 13.
    Kistler KD, Brunt EM, Clark JM, Diehl AM, Sallis JF, Schwimmer JB. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol. 2011;106(3):460–8. (quiz 469).CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology. 2009;49(1):80–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121–9.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Lazo M, Solga SF, Horska A, et al. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care. 2010;33(10):2156–2163.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery. Obesity (Silver Spring). 21(Suppl 1):S1–27.Google Scholar
  18. 18.
    Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Endocr Pract. 2013;19(2):337–72.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Jeffery RW, Wing RR. Long-term effects of interventions for weight loss using food provision and monetary incentives. J Consult Clin Psychol. 1995;63(5):793–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Diraison F, Yankah V, Letexier D, Dusserre E, Jones P, Beylot M. Differences in the regulation of adipose tissue and liver lipogenesis by carbohydrates in humans. J Lipid Res. 2003;44(4):846–53.CrossRefPubMedGoogle Scholar
  21. 21.
    Malik VS, Popkin BM, Bray GA, Despres JP, Hu FB. Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. Circulation. 2010;121(11):1356–64.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Maersk M, Belza A, Stodkilde-Jorgensen H, et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr. 2012;95(2):283–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Abdelmalek MF, Suzuki A, Guy C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology. 2010;51(6):1961–71.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Stanhope KL, Bremer AA, Medici V, et al. Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women. J Clin Endocrinol Metab. 2011;96(10):1596–1605.CrossRefGoogle Scholar
  25. 25.
    Ha V, Jayalath VH, Cozma AI, Mirrahimi A, de Souza RJ, Sievenpiper JL. Fructose-containing sugars, blood pressure, and cardiometabolic risk: a critical review. Curr Hypertens Rep. 2013;15(4):281–97.CrossRefPubMedGoogle Scholar
  26. 26.
    Silbernagel G, Machann J, Unmuth S, et al. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Br J Nutr. 2011;106(1):79–86.CrossRefPubMedGoogle Scholar
  27. 27.
    Aeberli I, Gerber PA, Hochuli M, et al. Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial. Am J Clin Nutr. 2011;94(2):479–85.CrossRefPubMedGoogle Scholar
  28. 28.
    Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein AH. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014;100(3):833–49.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lowndes J, Kawiecki D, Pardo S, et al. The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters. Nutr J. 2012;11:55.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Volek J, Sharman M, Gomez A, et al. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutr Metab. 2004;1(1):13.CrossRefGoogle Scholar
  31. 31.
    York LW, Puthalapattu S, Wu GY. Nonalcoholic fatty liver disease and low-carbohydrate diets. Annu Rev Nutr. 2009;29:365–79.CrossRefPubMedGoogle Scholar
  32. 32.
    Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003;348(21):2082–90.CrossRefPubMedGoogle Scholar
  33. 33.
    Saris WH, Astrup A, Prentice AM, et al. Randomized controlled trial of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates on body weight and blood lipids: the CARMEN study. The Carbohydrate Ratio Management in European National diets. Int J Obes Relat Metab Disord. 2000;24(10):1310–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Browning JD, Baker JA, Rogers T, Davis J, Satapati S, Burgess SC. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr. 2011;93(5):1048–52.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Westerbacka J, Lammi K, Hakkinen AM, et al. Dietary fat content modifies liver fat in overweight nondiabetic subjects. J Clin Endocrinol Metab. 2005;90(5):2804–2809.CrossRefPubMedGoogle Scholar
  36. 36.
    Knopp RH, Walden CE, Retzlaff BM, et al. Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The dietary alternatives study. JAMA. 1997;278(18):1509–15.CrossRefPubMedGoogle Scholar
  37. 37.
    Garg A, Grundy SM, Unger RH. Comparison of effects of high and low carbohydrate diets on plasma lipoproteins and insulin sensitivity in patients with mild NIDDM. Diabetes. 1992;41(10):1278–85.Google Scholar
  38. 38.
    Bozzetto L, Prinster A, Annuzzi G, et al. Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes Care. 2012;35(7):1429–1435.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Schwingshackl L, Hoffmann G. Monounsaturated fatty acids and risk of cardiovascular disease: synopsis of the evidence available from systematic reviews and meta-analyses. Nutrients. 2012;4(12):1989–2007.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Zivkovic AM, German JB, Sanyal AJ. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr. 2007;86(2):285–300.PubMedGoogle Scholar
  41. 41.
    Masterton GS, Plevris JN, Hayes PC. Review article: omega-3 fatty acids—a promising novel therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2010;31(7):679–92.CrossRefPubMedGoogle Scholar
  42. 42.
    Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77(5):1146–55.PubMedGoogle Scholar
  43. 43.
    Sofi F, Giangrandi I, Cesari F, et al. Effects of a 1-year dietary intervention with n-3 polyunsaturated fatty acid-enriched olive oil on non-alcoholic fatty liver disease patients: a preliminary study. Int J Food Sci Nutr. 2010;61(8):792–802.CrossRefPubMedGoogle Scholar
  44. 44.
    Riccardi G, Giacco R, Rivellese AA. Dietary fat, insulin sensitivity and the metabolic syndrome. Clin Nutr. 2004;23(4):447–56.CrossRefPubMedGoogle Scholar
  45. 45.
    Dasarathy S, Dasarathy J, Khiyami A, et al. Double-blind randomized placebo-controlled clinical trial of Omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014;49:137–44.CrossRefGoogle Scholar
  46. 46.
    Parker HM, Johnson NA, Burdon CA, Cohn JS, O’Connor HT, George J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;56(4):944–51.CrossRefPubMedGoogle Scholar
  47. 47.
    Sanyal AJ, Abdelmalek MF, Suzuki A, Cummings OW, Chojkier M, Group E-AS. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology. 2014;147(2):377–84 e371.CrossRefPubMedGoogle Scholar
  48. 48.
    Puri P, Baillie RA, Wiest MM, et al. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology. 2007;46(4):1081–90.CrossRefPubMedGoogle Scholar
  49. 49.
    Harris WS, Mozaffarian D, Rimm E, et al. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation. 2009;119(6):902–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Czernichow S, Thomas D, Bruckert E. n-6 Fatty acids and cardiovascular health: a review of the evidence for dietary intake recommendations. Br J Nutr. 2010;104(6):788–96.CrossRefPubMedGoogle Scholar
  51. 51.
    Yang HY, Tzeng YH, Chai CY, et al. Soy protein retards the progression of non-alcoholic steatohepatitis via improvement of insulin resistance and steatosis. Nutrition. 2011;27(9):943–8.CrossRefPubMedGoogle Scholar
  52. 52.
    Alkerwi A, Boutsen M, Vaillant M, et al. Alcohol consumption and the prevalence of metabolic syndrome: a meta-analysis of observational studies. Atherosclerosis. 2009;204(2):624–35.CrossRefPubMedGoogle Scholar
  53. 53.
    Sookoian S, Castano GO, Pirola CJ. Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals. Gut. 2014;63(3):530–2.CrossRefPubMedGoogle Scholar
  54. 54.
    Loomba R, Yang HI, Su J, et al. Synergism between obesity and alcohol in increasing the risk of hepatocellular carcinoma: a prospective cohort study. Am J Epidemiol. 2013;177(4):333–42.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Freedman ND, Everhart JE, Lindsay KL, et al. Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C. Hepatology. 2009;50(5):1360–9.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Gelatti U, Covolo L, Franceschini M, et al. Coffee consumption reduces the risk of hepatocellular carcinoma independently of its aetiology: a case-control study. J Hepatol. 2005;42(4):528–34.CrossRefPubMedGoogle Scholar
  57. 57.
    Bambha K, Wilson LA, Unalp A, et al. Coffee consumption in NAFLD patients with lower insulin resistance is associated with lower risk of severe fibrosis. Liver Int. 2013;38:1250–8.Google Scholar
  58. 58.
    Corrado RL, Torres DM, Harrison SA. Review of treatment options for nonalcoholic fatty liver disease. Med Clin N Am. 2014;98(1):55–72.CrossRefPubMedGoogle Scholar
  59. 59.
    Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675–85.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37–46.CrossRefPubMedGoogle Scholar
  61. 61.
    Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297(8):842–57.CrossRefPubMedGoogle Scholar
  62. 62.
    Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549–56.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Tamura Y, Tanaka Y, Sato F, et al. Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2005;90(6):3191–6.CrossRefPubMedGoogle Scholar
  64. 64.
    Sullivan S, Kirk EP, Mittendorfer B, Patterson BW, Klein S. Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease. Hepatology. 2012;55(6):1738–45.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009;50(4):1105–12.CrossRefPubMedGoogle Scholar
  66. 66.
    Pattyn N, Cornelissen VA, Eshghi SR, Vanhees L. The effect of exercise on the cardiovascular risk factors constituting the metabolic syndrome: a meta-analysis of controlled trials. Sports Med. 2013;43(2):121–33.CrossRefPubMedGoogle Scholar
  67. 67.
    Zelber-Sagi S, Buch A, Yeshua H, et al. Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial. World J Gastroenterol. 2014;20(15):4382–92.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Cornelissen VA, Fagard RH, Coeckelberghs E, Vanhees L. Impact of resistance training on blood pressure and other cardiovascular risk factors: a meta-analysis of randomized, controlled trials. Hypertension. 2011;58(5):950–8.CrossRefPubMedGoogle Scholar
  69. 69.
    Long M, Pedley A, Massaro JM. Non-alcoholic fatty liver disease is associated with lower levels of physical activity measured via Accelerometry: the Framingham Heart Study. Digestive Disease Week 2014. 2014; Chicago, Illinois.Google Scholar
  70. 70.
    George A St, Bauman A, Johnston A, Farrell G, Chey T, George J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2009;50(1):68–76.CrossRefGoogle Scholar
  71. 71.
    Garber CE, Blissmer B, Deschenes MR, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43(7):1334–1359.CrossRefPubMedGoogle Scholar
  72. 72.
    Organization WH. Global recommendations on physical activity for health 18–64 years old. 2014. Global recommendations on physical activity for health 2011. Accessed 8 July 2014.Google Scholar
  73. 73.
    Wing R. Behavioral weight control. In: Wadden TA, Stunkard AJ, editors. Handbook of obesity treatment. New York: Guilford; 2002. p. 301–316.Google Scholar
  74. 74.
    Shah K, Stufflebam A, Hilton TN, Sinacore DR, Klein S, Villareal DT. Diet and exercise interventions reduce intrahepatic fat content and improve insulin sensitivity in obese older adults. Obesity (Silver Spring). 2009;17(12):2162–8.CrossRefGoogle Scholar
  75. 75.
    Diabetes Prevention Program Research G. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care. 2002;25(12):2165–71.CrossRefGoogle Scholar
  76. 76.
    Ryan DH, Espeland MA, Foster GD, et al. Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes. Control Clin Trials. 2003;24(5):610–28.CrossRefPubMedGoogle Scholar
  77. 77.
    Frankenfield D, Roth-Yousey L, Compher C. Comparison of predictive equations for resting metabolic rate in healthy nonobese and obese adults: a systematic review. J Am Diet Assoc. 2005;105(5):775–89.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Center for Lifestyle MedicineNorthwestern MedicineChicagoUSA
  2. 2.Department of Gastroenterology and HepatologyNorthwestern University Feinberg School of MedicineChicagoUSA

Personalised recommendations