Skip to main content
SpringerLink
Log in

Current Prevention and Treatment Options for NAFLD

  • Chapter
  • First Online:
Obesity, Fatty Liver and Liver Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1061))

Abstract

Non-alcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease worldwide and the second leading indication for liver transplantation and the third leading cause of hepatocellular carcinoma (HCC) in the United States. This chapter focuses on the prevention and management of NAFLD. Healthy lifestyle is the cornerstone for the prevention and management of NAFLD and should be recommended to every patient at risk or having established NAFLD. Despite the high prevalence of NAFLD, it should be recognized that the majority of patients will not develop liver-related complications; cardiovascular disease remains the leading cause of death in NAFLD patients. Until further data are available, pharmacological treatment should be restricted to selected patients with confirmed non-alcoholic steatohepatitis. As some agents with primarily anti-fibrotic effect are currently being tested in NAFLD patients, significant fibrosis and cirrhosis may become additional indications for treatment in the future. Because of the surgical morbidity, currently bariatric surgery should only be performed in patients with morbid obesity, although the long-term impact of bariatric surgery on the histology of NAFLD is favorable.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.

    Article  PubMed  Google Scholar 

  2. Wong VW, Wong GL, Yeung DK, Lau TK, Chan CK, Chim AM, et al. Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy. J Hepatol. 2015;62:182–9.

    Article  PubMed  Google Scholar 

  3. Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–55.

    Article  PubMed  Google Scholar 

  4. Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62:1723–30.

    Article  PubMed  CAS  Google Scholar 

  5. Wong VW, Wong GL, Yeung JC, Fung CY, Chan JK, Chang ZH, et al. Long-term clinical outcomes after fatty liver screening in patients undergoing coronary angiogram: a prospective cohort study. Hepatology. 2016;63:754–63.

    Article  PubMed  Google Scholar 

  6. Wong VW, Chitturi S, Wong GL, Yu J, Chan HL, Farrell G. Pathogenesis and novel treatment options for non-alcoholic steatohepatitis. Lancet Gastroenterol Hepatol. 2016;1:56–67.

    Article  PubMed  Google Scholar 

  7. Brunt EM, Wong VW, Nobili V, Day CP, Sookoian S, Maher JJ, et al. Nonalcoholic fatty liver disease. Nat Rev Dis Primers. 2015;1:15080.

    Article  PubMed  Google Scholar 

  8. Wong VW, Chu WC, Wong GL, Chan RS, Chim AM, Ong A, et al. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut. 2012;61:409–15.

    Article  PubMed  Google Scholar 

  9. Wong VW, Chan RS, Wong GL, Cheung BH, Chu WC, Yeung DK, et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol. 2013;59:536–42.

    Article  PubMed  Google Scholar 

  10. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367–378 e365; quiz e314–365.

    Article  PubMed  Google Scholar 

  11. Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology. 2009;136:1552–60.

    Article  PubMed  CAS  Google Scholar 

  12. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359:229–41.

    Article  PubMed  CAS  Google Scholar 

  13. Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008;48:993–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Abdelmalek MF, Suzuki A, Guy C, Unalp-Arida A, Colvin R, Johnson RJ, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology. 2010;51:1961–71.

    Article  PubMed  CAS  Google Scholar 

  15. Basciano H, Federico L, Adeli K. Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond). 2005;2:5.

    Article  CAS  Google Scholar 

  16. Dunn W, Xu R, Schwimmer JB. Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease. Hepatology. 2008;47:1947–54.

    Article  PubMed  Google Scholar 

  17. Dunn W, Sanyal AJ, Brunt EM, Unalp-Arida A, Donohue M, McCullough AJ, et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol. 2012;57:384–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Wong VW, Wong GL, Chan HY, Yeung DK, Chan RS, Chim AM, et al. Bacterial endotoxin and non-alcoholic fatty liver disease in the general population: a prospective cohort study. Aliment Pharmacol Ther. 2015;42:731–40.

    Article  PubMed  CAS  Google Scholar 

  19. Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;57:157–66.

    Article  PubMed  CAS  Google Scholar 

  20. Oh S, Shida T, Yamagishi K, Tanaka K, So R, Tsujimoto T, et al. Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: a retrospective study. Hepatology. 2015;61:1205–15.

    Article  PubMed  CAS  Google Scholar 

  21. Ekelund U, Steene-Johannessen J, Brown WJ, Fagerland MW, Owen N, Powell KE, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet. 2016;388:1302–10.

    Article  PubMed  Google Scholar 

  22. Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005;82:222S–5S.

    Article  PubMed  CAS  Google Scholar 

  23. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–23.

    Article  PubMed  Google Scholar 

  24. European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–402.

    Google Scholar 

  25. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305:1659–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Sato K, Gosho M, Yamamoto T, Kobayashi Y, Ishii N, Ohashi T, et al. Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition. 2015;31:923–30.

    Article  PubMed  CAS  Google Scholar 

  28. 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;142:37–46.

    Article  PubMed  CAS  Google Scholar 

  29. Younossi ZM, Stepanova M, Rafiq N, Makhlouf H, Younoszai Z, Agrawal R, et al. Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology. 2011;53:1874–82.

    Article  PubMed  Google Scholar 

  30. Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547–54.

    Article  PubMed  CAS  Google Scholar 

  31. Angelico F, Burattin M, Alessandri C, Del Ben M, Lirussi F. Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis. Cochrane Database Syst Rev. 2007:CD005166.

    Google Scholar 

  32. Boettcher E, Csako G, Pucino F, Wesley R, Loomba R. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2012;35:66–75.

    Article  PubMed  CAS  Google Scholar 

  33. Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia. 2012;55:885–904.

    Article  PubMed  CAS  Google Scholar 

  34. Singh S, Khera R, Allen AM, Murad MH, Loomba R. Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: a systematic review and network meta-analysis. Hepatology. 2015;62:1417–32.

    Article  PubMed  CAS  Google Scholar 

  35. Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet. 2007;370:1129–36.

    Article  PubMed  CAS  Google Scholar 

  36. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–71.

    Article  PubMed  CAS  Google Scholar 

  37. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298:1180–8.

    Article  PubMed  CAS  Google Scholar 

  38. Lewis JD, Habel LA, Quesenberry CP, Strom BL, Peng T, Hedderson MM, et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. JAMA. 2015;314:265–77.

    Article  PubMed  CAS  Google Scholar 

  39. Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, 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;387:679–90.

    Article  PubMed  CAS  Google Scholar 

  40. Armstrong MJ, Hull D, Guo K, Barton D, Hazlehurst JM, Gathercole LL, et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J Hepatol. 2016;64:399–408.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Pellicciari R, Costantino G, Camaioni E, Sadeghpour BM, Entrena A, Willson TM, et al. Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid. J Med Chem. 2004;47:4559–69.

    Article  PubMed  CAS  Google Scholar 

  42. Xiong X, Wang X, Lu Y, Wang E, Zhang Z, Yang J, et al. Hepatic steatosis exacerbated by endoplasmic reticulum stress-mediated downregulation of FXR in aging mice. J Hepatol. 2014;60:847–54.

    Article  PubMed  CAS  Google Scholar 

  43. Fuchs M. Non-alcoholic fatty liver disease: the bile acid-activated farnesoid x receptor as an emerging treatment target. J Lipids. 2012;2012:934396.

    Article  PubMed  CAS  Google Scholar 

  44. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–65.

    Article  PubMed  CAS  Google Scholar 

  45. Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375:631–43.

    Article  PubMed  CAS  Google Scholar 

  46. French D, Liles JT, Liu H, Huntzicker EG, Djedjos CS, Kremoser C, et al. Pharmacodynamic effects of the non-steroidal farnesoid X receptor (FXR) agonist GS-9674 in high fat, high cholesterol diet fed cynomolgus monkeys. Hepatology. 2016;64(Suppl):71A.

    Google Scholar 

  47. Pawlak M, Lefebvre P, Staels B. Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2015;62:720–33.

    Article  PubMed  CAS  Google Scholar 

  48. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab. 2008;7:496–507.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Ratziu V, Harrison SA, Francque S, Bedossa P, Lehert P, Serfaty L, et al. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-alpha and -delta, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016;150:1147–1159 e1145.

    Article  PubMed  CAS  Google Scholar 

  50. Lefebvre E, Moyle G, Reshef R, Richman LP, Thompson M, Hong F, et al. Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis. PLoS One. 2016;11:e0158156.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Puengel T, Krenkel O, Mossanen J, Longerich T, Lefebvre E, Trautwein C, et al. The dual Ccr2/Ccr5 antagonist cenicriviroc ameliorates steatohepatitis and fibrosis in vivo by inhibiting the infiltration of inflammatory monocytes into injured liver. J Hepatol. 2016;64(Suppl):S160.

    Article  Google Scholar 

  52. Sanyal A, Ratziu V, Harrison S, Abdelmalek M, Aithal GP, Caballeria J, et al. Cenicriviroc vs placebo for the treatment of non-alcoholic steatohepatitis with liver fibrosis: results from the year 1 primary analysis of the phase 2b CENTAUR study. Hepatology. 2016;64(Suppl):1118A.

    Google Scholar 

  53. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 1997;275:90–4.

    Article  PubMed  CAS  Google Scholar 

  54. Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K, Takeda K, et al. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep. 2001;2:222–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002;16:1345–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, et al. GS-4997, an inhibitor of apoptosis signal-regulating kinase (ASK1), alone or in combination with simtuzumab for the treatment of nonalcoholic steatohepatitis (NASH): a randomized, phase 2 trial. Hepatology. 2016;64(Suppl):1119A.

    Google Scholar 

  57. Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379–88. quiz e315–376

    Article  PubMed  Google Scholar 

  58. Verbeek J, Lannoo M, Pirinen E, Ryu D, Spincemaille P, Vander Elst I, et al. Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis. Gut. 2015;64:673–83.

    Article  PubMed  CAS  Google Scholar 

  59. Klebanoff MJ, Corey KE, Chhatwal J, Kaplan LM, Chung RT, Hur C. Bariatric surgery for nonalcoholic steatohepatitis: a clinical and cost-effectiveness analysis. Hepatology. 2016.

    Google Scholar 

  60. Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, et al. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012;62:30–67.

    Article  PubMed  Google Scholar 

  61. Piguet AC, Saran U, Simillion C, Keller I, Terracciano L, Reeves HL, et al. Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis. J Hepatol. 2015;62:1296–303.

    Article  PubMed  CAS  Google Scholar 

  62. Donadon V, Balbi M, Mas MD, Casarin P, Zanette G. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int. 2010;30:750–8.

    Article  PubMed  CAS  Google Scholar 

  63. Chen HP, Shieh JJ, Chang CC, Chen TT, Lin JT, Wu MS, et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut. 2013;62:606–15.

    Article  PubMed  CAS  Google Scholar 

  64. El-Serag HB, Johnson ML, Hachem C, Morgana RO. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology. 2009;136:1601–8.

    Article  PubMed  CAS  Google Scholar 

  65. Hsiang JC, Wong GL, Tse YK, Wong VW, Yip TC, Chan HL. Statin and the risk of hepatocellular carcinoma and death in a hospital-based hepatitis B-infected population: a propensity score landmark analysis. J Hepatol. 2015;63:1190–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong

    Vincent Wai-Sun Wong

Authors
  1. Vincent Wai-Sun Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincent Wai-Sun Wong .

Editor information

Editors and Affiliations

  1. Institute of Digestive Disease and Department of Medicine & Therapeutics State Key Laboratory of Digestive Disease LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

    Jun Yu

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wong, V.WS. (2018). Current Prevention and Treatment Options for NAFLD. In: Yu, J. (eds) Obesity, Fatty Liver and Liver Cancer. Advances in Experimental Medicine and Biology, vol 1061. Springer, Singapore. https://doi.org/10.1007/978-981-10-8684-7_12

Download citation

Publish with us

Policies and ethics

Search

Navigation