Review Article | Published:

Management of NAFLD: a stage-based approach

Nature Reviews Gastroenterology & Hepatology volume 13, pages 196205 (2016) | Download Citation

Abstract

NAFLD is the most prevalent form of liver disease in the USA, affecting an estimated 30% of the population. The condition is associated with increased mortality related to cardiovascular disease, malignancy and liver disease. Identification of patients who might be at increased risk of adverse outcomes is critical as it is not feasible to screen all patients with suspected NAFLD. Patients with NASH, the progressive subtype of NAFLD, should be targeted for treatment, especially if they have concomitant fibrosis because such patients are more likely than those without fibrosis to have adverse outcomes. Treatment goals in patients with NAFLD vary depending on the disease stage owing to differential risk of progression and the particularities of an individual's comorbid disease. Lifestyle intervention is important for all patients irrespective of disease stage, but other therapies should be targeted to those most likely to benefit. In this Review, we highlight risk factors for disease progression and offer a stage-based treatment approach for patients with NAFLD.

Key points

  • NAFLD is the most common cause of liver disease, affecting 30% of the US population; however, the goals of treatment differ based on stage of disease

  • Lifestyle modification and excellent control of comorbid metabolic illness is important for all patients

  • Patients with NASH, the progressive subtype of NAFLD, should be targeted for treatment, especially if they have concomitant fibrosis because such patients are more likely to have adverse outcomes

  • Currently available pharmacological options include vitamin E, pioglitazone and pentoxifylline

  • Although bariatric surgery has not been studied prospectively specifically as a treatment for NASH, indirect evidence suggests it is effective at improving histological features of NASH, including fibrosis

  • Several promising drug therapies for NASH targeting a broad array of targets are in clinical trials and are anticipated to pave the way for new and more effective treatment options

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References

  1. 1.

    et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116, 1413–1419 (1999).

  2. 2.

    , & Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology 59, 2188–2195 (2014).

  3. 3.

    et al. A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J. Hepatol. 59, 550–556 (2013).

  4. 4.

    et al. Progression from isolated steatosis to steatohepatitis and fibrosis in nonalcoholic fatty liver disease. Clin. Res. Hepatol. Gastroenterol. 35, 23–28 (2011).

  5. 5.

    et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J. Hepatol. 62, 1148–1155 (2015).

  6. 6.

    et al. Liver fibrosis in overweight patients. Gastroenterology 118, 1117–1123 (2000).

  7. 7.

    , , & Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30, 1356–1362 (1999).

  8. 8.

    et al. Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy. Eur. J. Endocrinol. 167, 67–74 (2012).

  9. 9.

    , , & Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. Hepatology 39, 909–914 (2004).

  10. 10.

    et al. High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels. J. Clin. Endocrinol. Metab. (2014).

  11. 11.

    et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37, 1286–1292 (2003).

  12. 12.

    , , & Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann. Med. 43, 617–649 (2011).

  13. 13.

    et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 51, 1209–1217 (2010).

  14. 14.

    et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat. Commun. 5, 4309 (2014).

  15. 15.

    et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 61, 506–514 (2015).

  16. 16.

    et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149, 389–397. e10 (2015).

  17. 17.

    et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 61, 1547–1554 (2015).

  18. 18.

    et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 133, 481–488 (2007).

  19. 19.

    et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J. Hepatol. 50, 923–928 (2009).

  20. 20.

    et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 45, 846–854 (2007).

  21. 21.

    , , & Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 57, 1357–1365 (2013).

  22. 22.

    , , , & Transient elastography for the noninvasive assessment of liver fibrosis: a multicentre Canadian study. Can. J. Gastroenterol. 24, 661–670 (2010).

  23. 23.

    et al. Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: a prospective study. Hepatology 60, 1920–1928 (2014).

  24. 24.

    et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 142, 1592–1609 (2012).

  25. 25.

    et al. Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 38, 134–143 (2013).

  26. 26.

    et al. Plasma bile acids show a positive correlation with body mass index and are negatively associated with cognitive restraint of eating in obese patients. Front. Neurosci. 9, 199 (2015).

  27. 27.

    et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385, 956–965 (2015).

  28. 28.

    Longitudinal changes in FIB-4 and improvement in fibrosis stage with obeticholic acid: a secondary analysis of FLINT Trial. Presented at the American Academy for the Study of Liver Diseases 2015 Annual Meeting (2015).

  29. 29.

    et al. Fibrosis progression in nonalcoholic fatty liver versus nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin. Gastroenterol. Hepatol. 13, 643–654; e1–e9; quiz e39–e40 (2015).

  30. 30.

    et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–121 (2005).

  31. 31.

    et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44, 865–873 (2006).

  32. 32.

    et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial. J. Hepatol. 59, 536–542 (2013).

  33. 33.

    et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51, 121–129 (2010).

  34. 34.

    et al. Bariatric surgery reduces features of non-alcoholic steatohepatitis in morbidly obese patients. Gastroenterology 149, 379–388; quiz e15–e16 (2015).

  35. 35.

    et al. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am. J. Clin. Nutr. 93, 1048–1052 (2011).

  36. 36.

    et al. Alterations in hepatic glucose and energy metabolism as a result of calorie and carbohydrate restriction. Hepatology 48, 1487–1496 (2008).

  37. 37.

    et al. Refeeding with glucose rather than fructose elicits greater hepatic inflammatory gene expression in mice. Nutrition 31, 757–765 (2015).

  38. 38.

    et al. Impact of cholesterol metabolism and the LXRα–SREBP-1c pathway on nonalcoholic fatty liver disease. Int. J. Mol. Med. 23, 603–608 (2009).

  39. 39.

    et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand. J. Gastroenterol. 44, 471–477 (2009).

  40. 40.

    et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J. Am. Coll. Cardiol. 63, 2935–2959 (2014).

  41. 41.

    et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J. Hepatol. 59, 138–143 (2013).

  42. 42.

    et al. Weight loss via lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 149, 367–378 (2015).

  43. 43.

    , , , & Association of coffee drinking with total and cause-specific mortality. N. Engl. J. Med. 366, 1891–1904 (2012).

  44. 44.

    & Alcohol, smoking, coffee, and cirrhosis. Am. J. Epidemiol. 136, 1248–1257 (1992).

  45. 45.

    et al. Coffee consumption and reduced risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study. Cancer Causes Control 22, 503–510 (2011).

  46. 46.

    & Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology 128, 24–32 (2005).

  47. 47.

    et al. Regular coffee but not espresso drinking is protective against fibrosis in a cohort mainly composed of morbidly obese European women with NAFLD undergoing bariatric surgery. J. Hepatol. 57, 1090–1096 (2012).

  48. 48.

    et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 50, 1105–1112 (2009).

  49. 49.

    et al. Regular exercise is associated with a reduction in the risk of NAFLD and decreased liver enzymes in individuals with NAFLD independent of obesity in Korean adults. PLoS ONE 7, e46819 (2012).

  50. 50.

    et al. Effects of aerobic versus resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT. Am. J. Physiol. Endocrinol. Metab. 301, E1033–E1039 (2011).

  51. 51.

    et al. Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: a retrospective study. Hepatology 61, 1205–1215 (2014).

  52. 52.

    et al. Readiness for behaviour change in non-alcoholic fatty liver disease: implications for multidisciplinary care models. Liver Int. 35, 936–943 (2014).

  53. 53.

    , , , & Night eating syndrome: implications for severe obesity. Nutr. Diabetes 2, e44 (2012).

  54. 54.

    et al. The impact of sleep disorders on glucose metabolism: endocrine and molecular mechanisms. Diabetol. Metab. Syndr. 7, 25 (2015).

  55. 55.

    et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N. Engl. J. Med. 357, 741–752 (2007).

  56. 56.

    et al. Long-term mortality after gastric bypass surgery. N. Engl. J. Med. 357, 753–761 (2007).

  57. 57.

    Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am. J. Clin. Nutr. 55, 615S–619S (1992).

  58. 58.

    et al. Bariatric surgery improves histological features of nonalcoholic Fatty liver disease and liver fibrosis. J. Gastrointest. Surg. 19, 429–437 (2015).

  59. 59.

    et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 137, 532–540 (2009).

  60. 60.

    & Non-alcoholic fatty liver disease: is bariatric surgery the answer? Clin. Liver Dis. 13, 689–710 (2009).

  61. 61.

    et al. Rapid and body weight-independent improvement of endothelial and high-density lipoprotein function after Roux-en-Y gastric bypass: role of glucagon-like peptide-1. Circulation 131, 871–881 (2015).

  62. 62.

    et al. Mucosal glucagon-like peptide-1 and gastric inhibitory polypeptide cell numbers in the super-obese human foregut after gastric bypass. Surg. Obes. Relat. Dis. 11, 1237–1246 (2015).

  63. 63.

    et al. Hospital complication rates with bariatric surgery in Michigan. JAMA 304, 435–442 (2010).

  64. 64.

    , , , & Stomal complications of gastric bypass: incidence and outcome of therapy. Am. J. Gastroenterol. 87, 1165–1169 (1992).

  65. 65.

    , & Systematic review of bariatric surgery in patients with liver cirrhosis. Obes. Surg. 25, 1518–1526 (2015).

  66. 66.

    et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin. Gastroenterol. Hepatol. 2, 1107–1115 (2004).

  67. 67.

    et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 362, 1675–1685 (2010).

  68. 68.

    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 305, 1659–1668 (2011).

  69. 69.

    et al. CRN trials. Hepatology 62, 1 (2015).

  70. 70.

    3rd et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann. Intern. Med. 142, 37–46 (2005).

  71. 71.

    , , , & Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297, 842–857 (2007).

  72. 72.

    Unleashing the untold and misunderstood observations on vitamin E. Genes Nutr. 6, 5–16 (2011).

  73. 73.

    , , & Vitamin E supplementation and mortality in healthy people: a meta-analysis of randomised controlled trials. Cardiovasc. Drugs Ther. 28, 563–573 (2014).

  74. 74.

    et al. Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality. J. Nutr. Sci. Vitaminol. (Tokyo) 60, 194–205 (2014).

  75. 75.

    , & Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. PLoS ONE 8, e56803 (2013).

  76. 76.

    et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301, 39–51 (2009).

  77. 77.

    et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 301, 52–62 (2009).

  78. 78.

    , , , & Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ 341, c5702 (2010).

  79. 79.

    & Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease. Clin. Liver Dis. 8, 575–594 (2004).

  80. 80.

    , , , & The role of thiazolidinediones in non-alcoholic steatohepatitis — a systematic review and meta analysis. J. Hepatol. 55, 1383–1390 (2011).

  81. 81.

    , , , & Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone. Hepatology 38, 1008–1017 (2003).

  82. 82.

    et al. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann. Hepatol. 10, 277–286 (2011).

  83. 83.

    et al. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology 54, 1610–1619 (2011).

  84. 84.

    , , , & Health implications of high dietary omega-6 polyunsaturated fatty acids. J. Nutr. Metab. 2012, 539426 (2012).

  85. 85.

    et al. Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. Biochim. Biophys. Acta 1792, 1080–1086 (2009).

  86. 86.

    et al. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 46, 1081–1090 (2007).

  87. 87.

    et al. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology 147, 377–384. e1 (2014).

  88. 88.

    et al. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J. Hepatol. 62, 190–197 (2015).

  89. 89.

    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. 49, 137–144 (2015).

  90. 90.

    Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim. Biophys. Acta 1851, 469–484 (2015).

  91. 91.

    , & Anti-inflammatory effects of EPA and DHA are dependent upon time and dose-response elements associated with LPS stimulation in THP-1-derived macrophages. J. Nutr. Biochem. 21, 444–450 (2010).

  92. 92.

    & Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids. Acta Pharm. Sin. B 5, 129–134 (2015).

  93. 93.

    et al. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells. Hepatology 45, 695–704 (2007).

  94. 94.

    et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat. Med. 21, 159–165 (2015).

  95. 95.

    et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 145, 574–582. e1 (2013).

  96. 96.

    et al. Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase. J. Lipid Res. 47, 2754–2761 (2006).

  97. 97.

    et al. A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemia. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G543–G552 (2009).

  98. 98.

    et al. Farnesoid X receptor represses hepatic lipase gene expression. J. Lipid Res. 45, 2110–2115 (2004).

  99. 99.

    et al. Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia. J. Biol. Chem. 285, 3035–3043 (2010).

  100. 100.

    et al. HDL cholesterol efflux capacity and incident cardiovascular events. N. Engl. J. Med. 371, 2383–2393 (2014).

  101. 101.

    et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296, 1703–1706 (2002).

  102. 102.

    , , , & Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis. PLoS ONE 9, e108270 (2014).

  103. 103.

    & Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease. World J. Hepatol. 6, 570–579 (2014).

  104. 104.

    & Peroxisome proliferator-activated receptor δ: a multifaceted metabolic player. Curr. Opin. Lipidol. 24, 171–177 (2013).

  105. 105.

    et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 58, 1941–1952 (2013).

  106. 106.

    , , & Effects of the new dual PPAR α/δ agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism. Diabetes Care 34, 2008–2014 (2011).

  107. 107.

    et al. Dual peroxisome proliferator-activated receptor α/δ agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care 36, 2923–2930 (2013).

  108. 108.

    et al. An international, phase 2 randomized controlled trial of the dual PPAR alpha-delta aginist GFT505 in adult patients with NASH. Hepatology 62, 1 (2015).

  109. 109.

    et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet (2015).

  110. 110.

    Liraglutide is effective in the histological clearance of non-alcoholic steatohepatitis in a multicentre, double-blinded, randomised, placebo-controlled phase II trial. J. Hepatol. 62 (Suppl. 2) S187 (2015).

  111. 111.

    et al. Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis. J. Gastroenterol. Hepatol. 28, 450–455 (2013).

  112. 112.

    & Long-term therapy for chronic hepatitis B: hepatitis B virus DNA suppression leading to cirrhosis reversal. J. Gastroenterol. Hepatol. 28, 912–923 (2013).

  113. 113.

    , & Fibrosis — a common pathway to organ injury and failure. N. Engl. J. Med. 372, 1138–1149 (2015).

  114. 114.

    et al. Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology 60, 1645–1658 (2014).

  115. 115.

    et al. CCR2 antagonism in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Diabetes Obes. Metab. 16, 1055–1064 (2014).

  116. 116.

    , , & Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat. Rev. Immunol. 14, 181–194 (2014).

  117. 117.

    et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS ONE 8, e75361 (2013).

  118. 118.

    et al. Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 145, 782–789 (2013).

  119. 119.

    et al. Coffee consumption in NAFLD patients with lower insulin resistance is associated with lower risk of severe fibrosis. Liver Int. 34, 1250–1258 (2014).

  120. 120.

    et al. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology 55, 429–436 (2012).

  121. 121.

    et al. The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 12, 2085–2091. e2 (2014).

  122. 122.

    et al. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes. Acta Diabetol. 51, 865–873 (2014).

  123. 123.

    et al. The liver diseases of lipodystrophy: the long-term effect of leptin treatment. J. Hepatol. 59, 131–137 (2013).

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Affiliations

  1. Northwestern University Feinberg School of Medicine, Department of Internal Medicine, Division of Gastroenterology and Hepatology, 676 N. St. Clair Street, Arkes Pavillion, 14–005, Chicago, Illinois 60527, USA.

    • Mary E. Rinella
  2. Virginia Commonwealth University, 1200 East Broad Street, MCV BOX 980341, Richmond, Virginia 23298–0341, USA.

    • Arun J. Sanyal

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Contributions

All authors contributed equally to discussion of content, writing and reviewing/editing the manuscript before submission. M.E.R. researched data for the article.

Competing interests

M.E.R. has served as a consultant to AbbVie, FibroGen, Genentech, Intercept, NGM Biopharmaceuticals, NuSirt, Shire, Takeda and W.L Gore & Associates. A.J.S. has stock options in Genfit. He is the President of Sanyal Biotechnologies and has served as a consultant to AbbVie, Astra Zeneca, Boehringer Ingelhiem, Exalenz Bioscience, FibroGen, Genfit, Hemoshear, Immune Pharma, Immuron, Lilly, Nimbus Therapeutics, Nitto Denko, Salix Pharmaceuticals, Takeda and Tobira Therapeutics. He has been an unpaid consultant to Echosens and Intercept Pharmaceuticals. His institution has received grant support from Astra Zeneca, Bristol Myers, Gilead, Merck, Novartis, Salix Pharmaceuticals and Tobira Therapeutics.

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Correspondence to Arun J. Sanyal.

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https://doi.org/10.1038/nrgastro.2016.3

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