Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management

 

Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the United States, affecting up to 30% of adults. There are two forms of NAFLD: nonalcoholic fatty liver (NAFL), defined as 5% or greater hepatic steatosis without hepatocellular injury or fibrosis, and nonalcoholic steatohepatitis (NASH), defined as 5% or greater hepatic steatosis plus hepatocellular injury and inflammation, with or without fibrosis. Individuals with obesity are at highest risk of NAFLD. Other established risk factors include metabolic syndrome and type 2 diabetes mellitus. Although NAFLD is common and typically asymptomatic, screening is not currently recommended, even in high-risk patients. NAFLD should be suspected in patients with elevated liver enzymes or hepatic steatosis on abdominal imaging that are found incidentally. Once other causes, such as excessive alcohol use and hepatotoxic medications, are excluded in these patients, risk scores or elastography tests can be used to identify those who are likely to have fibrosis that will progress to cirrhosis. Liver biopsy should be considered for patients at increased risk of fibrosis and when other liver disorders cannot be excluded with noninvasive tests. Weight loss through diet and exercise is the primary treatment for NAFLD. Other treatments, such as bariatric surgery, vitamin E supplements, and pharmacologic therapy with thiazolidinediones or glucagon-like peptide-1 analogues, have shown potential benefit; however, data are limited, and these therapies are not considered routine treatments. NAFL typically follows an indolent course, whereas patients with NASH are at higher risk of death from cardiovascular disease, cancer, and end-stage liver disease.

Nonalcoholic fatty liver disease (NAFLD) comprises a continuum of fatty liver disease that occurs in the absence of alcohol use or other secondary causes of hepatic steatosis. There are two manifestations of NAFLD (Figure 1).1 One is nonalcoholic fatty liver (NAFL), which is defined as 5% or greater hepatic steatosis without evidence of hepatocellular injury or fibrosis. The other is nonalcoholic steatohepatitis (NASH), which is defined as 5% or greater hepatic steatosis with hepatocellular injury and inflammation, with or without fibrosis.1

WHAT'S NEW ON THIS TOPIC

It is projected that 100 million people in the United States will have nonalcoholic fatty liver disease by 2030, with direct medical costs of about $103 billion annually.

By 2030, nonalcoholic steatohepatitis is predicted to become the leading indication for liver transplantation in U.S. adults, surpassing hepatitis C.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments

Routine screening for NAFLD is not recommended, even for high-risk adults.1

C

Consensus guidelines; lack of evidence surrounding diagnosis, treatment, and benefit of screening

Patients with hepatic steatosis detected incidentally on imaging who have normal liver enzyme findings and no liver-related symptoms or signs should be assessed for metabolic risk factors (e.g., obesity, diabetes mellitus, dyslipidemia) and alternate causes of hepatic steatosis, such as excessive alcohol consumption or medication use.1,21

C

Consensus guidelines

Ultrasonography is the imaging test of choice for patients with suspected NAFLD.24,25

C

Limited-quality disease-oriented evidence

Noninvasive tools such as decision aids (NAFLD Fibrosis Score or Fibrosis-4 Score) or liver stiffness measurements using vibration-controlled elastography or magnetic resonance elastography are clinically useful for identifying patients with NAFLD who have a higher likelihood of developing fibrosis or cirrhosis.1,18,2729,35

C

Moderate-quality disease-oriented evidence

A liver biopsy should be offered to patients with NAFLD who are at increased risk of nonalcoholic steatohepatitis or advanced fibrosis based on noninvasive testing or if noninvasive testing cannot rule out other possible causes of chronic liver disease.1

C

Consensus guideline and usual practice

Weight loss through diet and exercise is the primary treatment for NAFLD. A loss of 7% to 10% of total body weight is needed to improve the histopathologic abnormalities in the liver associated with NAFLD.1

C

Consensus guidelines

There is insufficient evidence to support bariatric surgery, vitamin supplements, thiazolidinediones (pioglitazone [Actos]), and glucagon-like peptide-1 analogues (liraglutide [Victoza]) as first-line/primary treatments for NAFLD.1,6,21,3944,46,48

C

Low- to high-quality disease-oriented evidence from randomized controlled trials and expert opinion

Statins should be used to treat dyslipidemia in patients with NAFLD.1,21

C

Consensus guidelines and usual practice


NAFLD = nonalcoholic fatty liver disease.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C =

The Authors

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ERIN C. WESTFALL, DO, is an assistant professor at the University of Minnesota Medical School Mankato Family Medicine Residency, and is an adjunct assistant professor of family medicine at Mayo Clinic Medical School, Rochester, Minn....

ROBERT JESKE, MD, is an assistant professor at the University of Minnesota Medical School Mankato Family Medicine Residency.

ANDREW R. BADER, DO, is a family physician at Essentia Health–Baxter (Minn.) Clinic.

Address correspondence to Erin C. Westfall, DO, 101 Martin Luther King Jr. Dr., Mankato, MN 56001 (email: westfall.erin@mayo.edu). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

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1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–357....

2. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of non-alcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84.

3. Estes C, Anstee QM, Arias-Loste MT, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J Hepatol. 2018;69(4):896–904.

4. Sherif ZA, Saeed A, Ghavimi S, et al. Global epidemiology of nonalcoholic fatty liver disease and perspectives on US minority populations. Dig Dis Sci. 2016;61(5):1214–1225.

5. Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64(5):1577–1586.

6. Rinella ME. Nonalcoholic fatty liver disease: a systematic review [published correction appears in JAMA. 2015;314(14):1521]. JAMA. 2015;313(22):2263–2273.

7. Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547–555.

8. Abdelmalek MF, Diehl AM. Nonalcoholic fatty liver disease as a complication of insulin resistance. Med Clin North Am. 2007;91(6):1125–1149, ix.

9. Leite NC, Villela-Nogueira CA, Pannain VL, et al. Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors. Liver Int. 2011;31(5):700–706.

10. Fruci B, Giuliano S, Mazza A, et al. Nonalcoholic fatty liver: a possible new target for type 2 diabetes prevention and treatment. Int J Mol Sci. 2013;14(11):22933–22966.

11. Wu KT, Kuo PL, Su SB, et al. Nonalcoholic fatty liver disease severity is associated with the ratios of total cholesterol and triglycerides to high-density lipoprotein cholesterol. J Clin Lipidol. 2016;10(2):420–5.e1.

12. Lee SS, Byoun YS, Jeong SH, et al. Role of the PNPLA3 I148M polymorphism in nonalcoholic fatty liver disease and fibrosis in Korea. Dig Dis Sci. 2014;59(12):2967–2974.

13. Rosato V, Masarone M, Dallio M, et al. NAFLD and extra-hepatic comorbidities: current evidence on a multi-organ metabolic syndrome. Int J Environ Res Public Health. 2019;16(18):e3415.

14. Bayard M, Holt J, Boroughs E. Nonalcoholic fatty liver disease. Am Fam Physician. 2006;73(11):1961–1968. Accessed September 25, 2019. https://www.aafp.org/afp/2006/0601/p1961.html

15. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. [published corrections appear in Circulation. 2005;112(17):e297, and Circulation. 2005; 112(17):e298]. Circulation. 2005;112(17):2735–2752.

16. Corey KE, Klebanoff MJ, Tramontano AC, et al. Screening for nonalcoholic steatohepatitis in individuals with type 2 diabetes: a cost-effectiveness analysis. Dig Dis Sci. 2016;61(7):2108–2117.

17. Merck Manual Professional Version. Blood tests: normal values. Accessed September 2019. https://www.merckmanuals.com/professional/resources/normal-laboratory-values/blood-tests-normal-values

18. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6–19.

19. Kaswala DH, Lai M, Afdhal NH. Fibrosis assessment in nonalcoholic fatty liver disease (NAFLD) in 2016. Dig Dis Sci. 2016;61(5):1356–1364.

20. Rabinowich L, Shibolet O. Drug induced steatohepatitis: an uncommon culprit of a common disease. Biomed Res Int. 2015;2015:168905.

21. Glen J, Floros L, Day C, et al.; Guideline Development Group. Non-alcoholic fatty liver disease (NAFLD): summary of NICE guidance. BMJ. 2016;354:i4428.

22. Wilkins T, Tadkod A, Hepburn I, et al. Nonalcoholic fatty liver disease: diagnosis and management. Am Fam Physician. 2013;88(1):35–42. Accessed September 25, 2019. https://www.aafp.org/afp/2013/0701/p35

23. Jennison E, Patel J, Scorletti E, et al. Diagnosis and management of non-alcoholic fatty liver disease. Postgrad Med J. 2019;95(1124):314–322.

24. Hernaez R, Lazo M, Bonekamp S, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54(3):1082–1090.

25. Ballestri S, Nascimbeni F, Baldelli E, et al. Ultrasonographic fatty liver indicator detects mild steatosis and correlates with metabolic/histological parameters in various liver diseases. Metabolism. 2017;72:57–65.

26. Ferraioli G, Soares Monteiro LB. Ultrasound-based techniques for the diagnosis of liver steatosis. World J Gastroenterol. 2019;25(40):6053–6062.

27. Imajo K, Kessoku T, Honda Y, et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology. 2016;150(3):626–637.e7.

28. Hsu C, Caussy C, Imajo K, et al. Magnetic resonance vs transient elastography analysis of patients with nonalcoholic fatty liver disease: a systematic review and pooled analysis of individual participants. Clin Gastroenterol Hepatol. 2019;17(4):630–637.e8.

29. McPherson S, Anstee QM, Henderson E, et al. Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels? Eur J Gastroenterol Hepatol. 2013;25(6):652–658.

30. Tapper EB, Challies T, Nasser I, et al. The performance of vibration controlled transient elastography in a US cohort of patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2016;111(5):677–684.

31. Sattar N, Forrest E, Preiss D. Non-alcoholic fatty liver disease. BMJ. 2014;349:g4596.

32. Osayande AS, Kale N. Nonalcoholic fatty liver disease: identifying patients at risk of inflammation or fibrosis. Am Fam Physician. 2017;95(12):796–797. Accessed September 25, 2019. https://www.aafp.org/afp/2017/0615/p796.html

33. Thampanitchawong P, Piratvisuth T. Liver biopsy: complications and risk factors. World J Gastroenterol. 1999;5(4):301–304.

34. Singh S, Allen AM, Wang Z, et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643–54.e1.

35. Wright AP, Desai AP, Bajpai S, et al. Gaps in recognition and evaluation of incidentally identified hepatic steatosis. Dig Dis Sci. 2015;60(2):333–338.

36. Park CC, Nguyen P, Hernandez C, et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology. 2017;152(3):598–607.e2.

37. Zelber-Sagi S, Salomone F, Mlynarsky L. The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: evidence and plausible mechanisms. Liver Int. 2017;37(7):936–949.

38. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–1402.

39. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379–388.

40. Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis [published correction appears in JAMA. 2008;299(7):765–766]. JAMA. 2007;297(8):842–857.

41. Gee PT. Unleashing the untold and misunderstood observations on vitamin E. Genes Nutr. 2011;6(1):5–16.

42. Schürks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010;341:c5702.

43. 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):1549–1556.

44. Bjelakovic G, Nikolova D, Bjelakovic M, et al. Vitamin D supplementation for chronic liver diseases in adults. Cochrane Database Syst Rev. 2017;(11):CD011564.

45. Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142(4):711–725.e6.

46. Sanyal AJ, Chalasani N, Kowdley KV, et al.; NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675–1685.

47. Mantovani A, Byrne CD, Scorletti E, et al. Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: an updated systematic review of randomized controlled trials [published online January 7, 2020]. Diabetes Metab. Accessed April 2, 2020. https://www.sciencedirect.com/science/article/abs/pii/S1262363620300021

48. Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679–690.

49. Boursier J, Vergniol J, Guillet A, et al. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol. 2016;65(3):570–578.

50. Italian Association for the Study of the Liver (AISF). AISF position paper on nonalcoholic fatty liver disease (NAFLD): updates and future directions. Dig Liver Dis. 2017;49(5):471–483.

51. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723–750.

52. Torres DM, Williams CD, Harrison SA. Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012;10(8):837–858.

53. Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–121.

54. Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol. 2008;49(4):608–612.

55. Musso G, Gambino R, Cassader M, et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617–649.

56. Goh GB, McCullough AJ. Natural history of nonalcoholic fatty liver disease. Dig Dis Sci. 2016;61(5):1226–1233.

57. McPherson S, Stewart SF, Henderson E, et al. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265–1269.

 

 

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