Hepatic steatosis - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common causes of chronic liver disease in the developed world.
It is a spectrum of disease, ranging from hepatic fat accumulation without inflammation to steatohepatitis, fibrosis, cirrhosis, and end-stage liver disease.
MASLD is considered the hepatic manifestation of metabolic syndrome and is associated with obesity, dyslipidemia, and type 2 diabetes mellitus.
The diagnosis of MASLD is based on exclusion of other etiologies of steatotic liver disease, such as alcohol use, and supportive laboratory tests and imaging. Liver biopsy and histology is the gold standard for diagnosis, and is performed for patients at higher risk of fibrosis or steatohepatitis.
Lifestyle modification, including weight loss, physical activity, and dietary changes, is the first-line therapy. There are no licensed drug treatments, although use of pioglitazone or vitamin E may be considered for selected patients.

A wedge biopsy of the liver from a 52-year-old female organ donor; the biopsy shows moderate mixed micro- and macrovesicular steatosis; there is no significant lobular inflammation or necrosis (hematoxylin and eosin, [H&E] stain, x 200)

From the collection of Kapil B. Chopra, MD

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Definition

Epidemiology

Etiology

Pathophysiology

Images

A wedge biopsy of the liver from a 52-year-old female organ donor; the biopsy shows moderate mixed micro- and macrovesicular steatosis; there is no significant lobular inflammation or necrosis (hematoxylin and eosin, [H&E] stain, x 200)
A case of metabolic dysfunction-associated steatohepatitis; the biopsy shows ballooning degeneration of the hepatocytes (middle right) and spotty lobular inflammation in addition to mixed micro- and macrovesicular steatosis (H&E, x 200)
A native hepatectomy specimen from a patient with a history of metabolic dysfunction-associated steatohepatitis; a cross-section of the liver shows mixed, predominantly micronodular cirrhosis; the orange-yellow color of the nodules is due to moderate mixed micro- and macrovesicular steatosis involving 40% of the liver parenchyma

Citations

Key Articles

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-835.[Abstract][Full Text]
Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):319-34.[Abstract][Full Text]
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 Jun;64(6):1388-402.[Abstract][Full Text]
Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35.[Abstract][Full Text]
LaBrecque DR, Abbas Z, Anania F, et al; World Gastroenterology Association. World Gastroenterology Organisation global guidelines: nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014 Jul;48(6):467-73.[Abstract][Full Text]

Other Online Resources

NAFLD Fibrosis Score
Fibrosis 4 Score (FIB-4)
MELD calculator
NIH: nonalcoholic fatty liver disease and NASH

Referenced Articles

1. Kanwal F, Neuschwander-Tetri BA, Loomba R, et al. Metabolic dysfunction-associated steatotic liver disease: update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease. Hepatology. 2024 May 1;79(5):1212-9.[Abstract][Full Text]
2. American Association for the Study of Liver Diseases. New MASLD nomenclature. Jun 2023 [internet publication].[Full Text]
3. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-835.[Abstract][Full Text]
4. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001;21(1):3-16.[Abstract]
5. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21.[Abstract][Full Text]
6. Duell PB, Welty FK, Miller M, et al; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; Council on the Kidney in Cardiovascular Disease; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease. Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2022 Jun;42(6):e168-85.[Abstract][Full Text]
7. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84.[Abstract][Full Text]
8. Wong VW, Chan WK, Chitturi S, et al. Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017 - part 1: definition, risk factors and assessment. J Gastroenterol Hepatol. 2018 Jan;33(1):70-85.[Abstract][Full Text]
9. Allen AM, Therneau TM, Larson JJ, et al. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study. Hepatology. 2018 May;67(5):1726-36.[Abstract]
10. Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):319-34.[Abstract][Full Text]
11. Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988-1994 to 2007-2010. J Pediatr. 2013 Mar;162(3):496-500.e1.[Abstract]
12. Balakrishnan M. Women have a lower risk of nonalcoholic fatty liver disease but higher risk of nonalcoholic fatty liver disease fibrosis than men: summary of the findings of a systematic review and meta-analysis. Clin Liver Dis (Hoboken). 2021 Nov;18(5):251-4.[Abstract][Full Text]
13. Shaheen M, Schrode KM, Pan D, et al. Sex-specific differences in the association between race/ethnicity and NAFLD among US population. Front Med (Lausanne). 2021;8:795421.[Abstract][Full Text]
14. 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 May;61(5):1214-25.[Abstract]
15. Sanyal AJ, Van Natta ML, Clark J, et al. Prospective study of outcomes in adults with nonalcoholic fatty liver disease. N Engl J Med. 2021 Oct 21;385(17):1559-69.[Abstract]
16. Ludwig J, Viggiano TR, McGill DB, et al. Non-alcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980 Jul;55(7):434-8.[Abstract]
17. Griffen WO Jr, Bivins BA, Bell RM. The decline and fall of the jejunoileal bypass. Surg Gynecol Obstet. 1983 Oct;157(4):301-8.[Abstract]
18. Eslam M, Sanyal AJ, George J, et al. MAFLD: a consensus-driven proposed momenclature for metabolic associated fatty liver disease. Gastroenterology. 2020 May;158(7):1999-2014.e1.[Abstract]
19. Edmison J, McCullough AJ. Pathogenesis of non-alcoholic steatohepatitis: human data. Clin Liver Dis. 2007 Feb;11(1):75-104;ix.[Abstract]
20. Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022 May;28(5):528-62.[Abstract][Full Text]
21. St-Onge MP, Janssen I, Heymsfield SB. Metabolic syndrome in normal weight Americans. Diabetes Care. 2004 Sep;27(9):2222-8.[Abstract][Full Text]
22. Ong JP, Elariny H, Collantes R, et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg. 2005 Mar;15(3):310-5.[Abstract]
23. Bazick J, Donithan M, Neuschwander-Tetri BA, et al. Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: guidelines for referral in NAFLD. Diabetes Care. 2015;38:1347-1355.[Abstract][Full Text]
24. Chitturi S, Abeygunasekera S, Farrell GC, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002 Feb;35(2):373-9.[Abstract][Full Text]
25. Assy N, Kaita K, Mymin D, et al. Fatty infiltration of liver in hyperlipidemic patients. Dig Dis Sci. 2000 Oct;45(10):1929-34.[Abstract]
26. Donati G, Stagni B, Piscaglia F, et al. Increased prevalence of fatty liver in arterial hypertensive patients: role of insulin resistance. Gut. 2004 Jul;53(7):1020-3.[Abstract][Full Text]
27. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003 Apr;37(4):917-23.[Abstract][Full Text]
28. Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005 Nov 15;143(10):722-8.[Abstract]
29. Styblo T, Martin S, Kaminski DL. The effects of reversal of jejunoileal bypass operations on hepatic triglyceride content and hepatic morphology. Surgery. 1984 Oct;96(4):632-41.[Abstract]
30. Fontana RJ, Liou I, Reuben A, et al. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury. Hepatology. 2022 Jul 27 [Epub ahead of print].[Abstract][Full Text]
31. Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology. 2006 Feb;130(2 suppl 1):S70-7.[Abstract]
32. Wattacheril JJ, Abdelmalek MF, Lim JK, et al. AGA clinical practice update on the role of noninvasive biomarkers in the evaluation and management of nonalcoholic fatty liver disease: expert review. Gastroenterology. 2023 Oct;165(4):1080-8.[Abstract][Full Text]
33. Sterling RK, Duarte-Rojo A, Patel K, et al. AASLD practice guideline on imaging-based non-invasive liver disease assessments of hepatic fibrosis and steatosis. Hepatology. 15 Mar 2024 [Epub ahead of print].[Abstract][Full Text]
34. Sterling RK, Patel K, Duarte-Rojo A, et al. AASLD practice guideline on blood-based non-invasive liver disease assessments of hepatic fibrosis and steatosis. Hepatology. 15 Mar 2024 [Epub ahead of print].[Abstract][Full Text]
35. Kaplan DE, Ripoll C, Thiele M, et al. AASLD practice guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology. 2024 May 1;79(5):1180-211.[Abstract][Full Text]
36. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002 Apr 18;346(16):1221-31.[Abstract]
37. Sharma P, Arora A. Clinical presentation of alcoholic liver disease and non-alcoholic fatty liver disease: spectrum and diagnosis. Transl Gastroenterol Hepatol. 2020;5:19.[Abstract][Full Text]
38. Bacon BR, Faravash MJ, Janney CG, et al. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994 Oct;107(4):1103-9.[Abstract]
39. Liangpunsakul S, Chalasani N. What should we recommend to our patients with NAFLD regarding alcohol use? Am J Gastroenterol. 2012 Jul;107(7):976-8.[Abstract][Full Text]
40. 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 Jun;64(6):1388-402.[Abstract][Full Text]
41. Long MT, Noureddin M, Lim JK. AGA Clinical practice update: diagnosis and management of nonalcoholic fatty liver disease in lean individuals: expert review. Gastroenterology. 2022 Sep;163(3):764-74.e1.[Abstract][Full Text]
42. Liu CJ. Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese. J Gastroenterol Hepatol. 2012 Oct;27(10):1555-60.[Abstract][Full Text]
43. Diehl AM, Goodman Z, Ishak KG. Alcohol-like liver disease in nonalcoholics: a clinical and histological comparison with alcohol-induced liver injury. Gastroenterology. 1988 Oct;95(4):1056-62.[Abstract]
44. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35.[Abstract][Full Text]
45. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003 Jun;37(6):1286-92.[Abstract][Full Text]
46. Angulo P, Lindor KD. Non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2002 Feb;(suppl 17):S186-90.[Abstract]
47. Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999 Dec;30(6):1356-62.[Abstract]
48. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology. 2009 Jan;49(1):306-17.[Abstract][Full Text]
49. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a non-invasive system that indentifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846-854.[Abstract][Full Text]
50. McPherson S, Armstrong MJ, Cobbold JF, et al. Quality standards for the management of non-alcoholic fatty liver disease (NAFLD): consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group. Lancet Gastroenterol Hepatol. 2022 Aug;7(8):755-69.[Abstract][Full Text]
51. Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009 Oct;7(10):1104-12.[Abstract][Full Text]
52. European Association for the Study of the Liver. EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol. 2021 Sep;75(3):659-89.[Abstract][Full Text]
53. Idilman IS, Aniktar H, Idilman R, et al. Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiology. 2013 Jun;267(3):767-75.[Abstract][Full Text]
54. 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 Feb;152(3):598-607.e2.[Abstract]
55. American College of Radiology. ACR appropriateness criteria: chronic liver disease. 2019 [internet publication].[Full Text]
56. Dowman JK, Tomlinson JW, Newsome PN. Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2011 Mar;33(5):525-40.[Abstract][Full Text]
57. Tahan V, Canbakan B, Balci H, et al. Serum gamma-glutamyltranspeptidase distinguishes non-alcoholic fatty liver disease at high risk. Hepatogastroenterology. 2008 Jul-Aug;55(85):1433-8.[Abstract]
58. Angeli P, Wong F, Watson H, et al. Hyponatremia in cirrhosis: results of a patient population survey. Hepatology. 2006 Dec;44(6):1535-42.[Abstract][Full Text]
59. Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008 Sep 4;359(10):1018-26.[Abstract][Full Text]
60. Cotler SJ, Kanji K, Keshavarzian A, et al. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol. 2004 Oct;38(9):801-4.[Abstract]
61. Chitturi S, Weltman M, Farreel G, et al. HFE mutations, hepatic iron and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. Hepatology. 2002 Jul;36(1):142-9.[Abstract][Full Text]
62. Yilmaz Y. Systematic review: caspase-cleaved fragments of cytokeratin 18 - the promises and challenges of a biomarker for chronic liver disease. Aliment Pharmacol Ther. 2009 Dec 1;30(11-12):1103-9.[Abstract][Full Text]
63. Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol. 2004 Apr;40(4):578-84.[Abstract]
64. Muratori L, Granito A, Muratori P, et al. Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value. Clin Liver Dis. 2008 May;12(2):261-76;vii.[Abstract]
65. Powell EE, Cooksley WG, Hanson R, et al. The natural history of nonalcoholic steatohepatitis: a follow-up of forty-two patients for up to 21 years. Hepatology. 1990 Jan;11(1):74-80.[Abstract]
66. National Institute for Health and Care Excellence. Non-alcoholic fatty liver disease (NAFLD): assessment and management. Jul 2016 [internet publication].[Full Text]
67. Chitturi S, Wong VW, Chan WK, et al. The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017 - part 2: management and special groups. J Gastroenterol Hepatol. 2018 Jan;33(1):86-98.[Abstract][Full Text]
68. Sterling RK, Asrani SK, Levine D, et al. AASLD practice guideline on non-invasive liver disease assessments of portal hypertension. Hepatology. 2024 Mar 15.[Abstract][Full Text]
69. American College of Radiology. ACR appropriateness criteria®: abnormal liver function tests. 2023 [internet publication].[Full Text]
70. LaBrecque DR, Abbas Z, Anania F, et al; World Gastroenterology Association. World Gastroenterology Organisation global guidelines: nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014 Jul;48(6):467-73.[Abstract][Full Text]
71. Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012 Jan;56(1):255-66.[Abstract][Full Text]
72. Keating SE, Hackett DA, George J, et al. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012 Jul;57(1):157-66.[Abstract]
73. Younossi ZM, Reyes MJ, Mishra A, et al. Systematic review with meta-analysis: non-alcoholic steatohepatitis - a case for personalised treatment based on pathogenic targets. Aliment Pharmacol Ther. 2014 Jan;39(1):3-14.[Abstract][Full Text]
74. Zelber-Sagi S, Kessler A, Brazowsky E, et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006 May;4(5):639-44.[Abstract]
75. Zeng MD, Fan JG, Lu LG, et al. Guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases. J Dig Dis. 2008 May;9(2):108-12.[Abstract]
76. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015 Aug;149(2):367-78.e5; quiz e14-5.[Abstract][Full Text]
77. Musso G, Cassader M, Rosina F, et al. 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 Apr;55(4):885-904.[Abstract][Full Text]
78. Bacchi E, Negri C, Targher G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial). Hepatology. 2013 Oct;58(4):1287-95.[Abstract][Full Text]
79. St George A, Bauman A, Johnston A, et al. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2009 Jul;50(1):68-76.[Abstract][Full Text]
80. Buzzetti E, Linden A, Best LM, et al. Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Jun 11;6:CD013156.[Abstract][Full Text]
81. Jarvis H, O'Keefe H, Craig D, et al. Does moderate alcohol consumption accelerate the progression of liver disease in NAFLD? A systematic review and narrative synthesis. BMJ Open. 2022 Jan 4;12(1):e049767.[Abstract][Full Text]
82. Wang H, Wang L, Cheng Y, et al. Efficacy of orlistat in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Biomed Rep. 2018 Jul;9(1):90-6.[Abstract][Full Text]
83. Xanthakos SA, Jenkins TM, Kleiner DE, et al. High prevalence of nonalcoholic fatty liver disease in adolescents undergoing bariatric surgery. Gastroenterology. 2015 Sep;149(3):623-34;e8.[Abstract][Full Text]
84. Fakhry TK, Mhaskar R, Schwitalla T, et al. Bariatric surgery improves nonalcoholic fatty liver disease: a contemporary systematic review and meta-analysis. Surg Obes Relat Dis. 2019 Mar;15(3):502-11.[Abstract]
85. Lee Y, Doumouras AG, Yu J, et al. Complete resolution of nonalcoholic fatty liver disease after bariatric surgery: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019 May;17(6):1040-60;e11.[Abstract][Full Text]
86. Chavez-Tapia NC, Tellez-Avila FI, Barrientos-Gutierrez T, et al. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD007340.[Abstract][Full Text]
87. Boettcher E, Csako G, Pucino F, et al. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2012 Jan;35(1):66-75.[Abstract][Full Text]
88. Said A, Akhter A. Meta-analysis of randomized controlled trials of pharmacologic agents in non-alcoholic steatohepatitis. Ann Hepatol. 2017 Jul-Aug;16(4):538-47.[Abstract]
89. Sawangjit R, Chongmelaxme B, Phisalprapa P, et al. Comparative efficacy of interventions on nonalcoholic fatty liver disease (NAFLD): a PRISMA-compliant systematic review and network meta-analysis. Medicine (Baltimore). 2016 Aug;95(32):e4529.[Abstract][Full Text]
90. Mahady SE, Webster AC, Walker S, et al. The role of thiazolidinediones in non-alcoholic steatohepatitis: a systematic review and meta analysis. J Hepatol. 2011 Dec;55(6):1383-90.[Abstract]
91. Mantovani A, Byrne CD, Targher G. Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. Lancet Gastroenterol Hepatol. 2022 Apr;7(4):367-78.[Abstract]
92. Lutchman G, Modi A, Kleiner DE, et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology. 2007 Aug;46(2):424-9.[Abstract][Full Text]
93. Musso G, Cassader M, Paschetta E, et al. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis. JAMA Intern Med. 2017 May 1;177(5):633-40.[Abstract][Full Text]
94. McDonough AK, Rosenthal RS, Cao X, et al. The effect of thiazolidinediones on BMD and osteoporosis. Nat Clin Pract Endocrinol Metab. 2008 Sep;4(9):507-13.[Abstract]
95. 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 Sep 29;370(9593):1129-36.[Abstract]
96. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, et al. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 2003 Oct;38(4):1008-17.[Abstract]
97. Ratziu V, Giral P, Jacqueminet S, et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) trial. Gastroenterology. 2008;135:100-110.[Abstract]
98. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71.[Abstract][Full Text]
99. Sato K, Gosho M, Yamamoto T, et al. Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition. 2015 Jul-Aug;31(7-8):923-30.[Abstract]
100. Ji HF, Sun Y, Shen L. Effect of vitamin E supplementation on aminotransferase levels in patients with NAFLD, NASH, and CHC: results from a meta-analysis. Nutrition. 2014 Sep;30(9):986-91.[Abstract]
101. Vilar-Gomez E, Vuppalanchi R, Gawrieh S, et al. Vitamin E improves transplant-free survival and hepatic decompensation among patients with nonalcoholic steatohepatitis and advanced fibrosis. Hepatology. 2018 Dec 1.[Abstract]
102. 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. JAMA. 2007 Feb 28;297(8):842-57.[Abstract]
103. Schürks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010 Nov 4;341:c5702.[Abstract][Full Text]
104. 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 Oct 12;306(14):1549-56.[Abstract][Full Text]
105. Mantovani A, Csermely A, Petracca G, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021 Nov;6(11):903-13.[Abstract]
106. Athyros VG, Tziomalos K, Gossios TD, et al. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet. 2010 Dec 4;376(9756):1916-22.[Abstract]
107. Pastori D, Pani A, Di Rocco A, et al. Statin liver safety in non-alcoholic fatty liver disease: a systematic review and metanalysis. Br J Clin Pharmacol. 2022 Feb;88(2):441-51.[Abstract][Full Text]
108. Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology. 2005 Apr;41(4):690-5.[Abstract][Full Text]
109. Eslami L, Merat S, Malekzadeh R, et al. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database Syst Rev. 2013 Dec 27;(12):CD008623.[Abstract][Full Text]
110. Foster T, Budoff MJ, Saab S, et al. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol. 2011 Jan;106(1):71-7.[Abstract]
111. Shyangdan D, Clar C, Ghouri N, et al. Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic review. Health Technol Assess. 2011 Nov;15(38):1-110.[Abstract][Full Text]
112. Li Y, Liu L, Wang B, et al. Metformin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Biomed Rep. 2013 Jan;1(1):57-64.[Abstract][Full Text]
113. Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxycholic acid for the treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004 Mar;39(3):770-8.[Abstract][Full Text]
114. Leuschner UF, Lindenthal B, Herrmann G, et al. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blinded randomized, placebo-controlled trial. Hepatology. 2010 Aug;52(2):472-9.[Abstract][Full Text]
115. Boyer TD, Haskal ZJ, American Association for the Study of Liver Diseases. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension: update 2009. Hepatology. 2010 Jan;51(1):306.[Abstract][Full Text]
116. Angulo P. Nonalcoholic fatty liver disease and liver transplantation. Liver Transpl. 2006 Apr;12(4):523-34.[Abstract][Full Text]
117. Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011 Oct;141(4):1249-53.[Abstract]
118. Malik SM, deVera ME, Fontes P, et al. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant. 2009 Apr;9(4):782-93.[Abstract][Full Text]
119. Vanwagner LB, Bhave M, Te HS, et al. Patients transplanted for nonalcoholic steatohepatitis (NASH) are at increased risk for post-operative cardiovascular events. Hepatology. 2012 Nov;56(5):1741-50.[Abstract][Full Text]
120. Tsochatzis E, Coilly A, Nadalin S, et al. International liver transplantation consensus statement on end-stage liver disease due to nonalcoholic steatohepatitis and liver transplantation. Transplantation. 2019 Jan;103(1):45-56.[Abstract]
121. Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024 Feb 8;390(6):497-509.[Abstract][Full Text]
122. ClinicalTrials.gov. A phase 3 study to evaluate the efficacy and safety of MGL-3196 (Resmetirom) in patients with NASH and fibrosis (MAESTRO-NASH). ClinicalTrials.gov Identifier: NCT03900429. Feb 2024 [internet publication].[Full Text]
123. Harrison SA, Ruane PJ, Freilich BL, et al. Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial. Nat Med. 2021 Jul;27(7):1262-71.[Abstract][Full Text]
124. Harrison SA, Frias JP, Neff G, et al. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2023 Dec;8(12):1080-93.[Abstract][Full Text]
125. Loomba R, Sanyal AJ, Kowdley KV, et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH. N Engl J Med. 2023 Sep 14;389(11):998-1008.[Abstract][Full Text]
126. ClinicalTrials.gov. A study evaluating the efficacy and safety of pegozafermin in participants with MASH and fibrosis (ENLIGHTEN-Fibrosis). ClinicalTrials.gov Identifier: NCT06318169. Jun 2024 [internet publication].[Full Text]
127. Abdelmalek MF, Charles ED, Sanyal AJ, et al. The FALCON program: two phase 2b randomized, double-blind, placebo-controlled studies to assess the efficacy and safety of pegbelfermin in the treatment of patients with nonalcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis. Contemp Clin Trials. 2021 May;104:106335.[Abstract][Full Text]
128. Abdelmalek MF, Sanyal AJ, Nakajima A, et al. Pegbelfermin in patients with nonalcoholic steatohepatitis and compensated cirrhosis (FALCON 2): a randomized phase 2b study. Clin Gastroenterol Hepatol. 2024 Jan;22(1):113-23.e9.[Abstract][Full Text]
129. Loomba R, Sanyal AJ, Nakajima A, et al. Pegbelfermin in patients with nonalcoholic steatohepatitis and stage 3 fibrosis (FALCON 1): a randomized phase 2b study. Clin Gastroenterol Hepatol. 2024 Jan;22(1):102-12.e9.[Abstract][Full Text]
130. Sanyal A, Charles ED, Neuschwander-Tetri BA, et al. Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet. 2019 Dec 22;392(10165):2705-17.[Abstract]
131. Francque SM, Bedossa P, Ratziu V, et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH. N Engl J Med. 2021 Oct 21;385(17):1547-58.[Abstract][Full Text]
132. Clinicaltrials.gov. A phase 3 study evaluating long-term efficacy and safety of lanifibranor in adult patients with (NASH) and fibrosis 2 (F2)/fibrosis 3 (F3) stage of liver fibrosis (NATiV3). Mar 2022 [internet publication].[Full Text]
133. Singh S, Khera R, Allen AM, et al. Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: a systematic review and network meta-analysis. Hepatology. 2015 Nov;62(5):1417-32.[Abstract][Full Text]
134. Sanyal AJ, Ratziu V, Loomba R, et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. J Hepatol. 2023 Nov;79(5):1110-20.[Abstract][Full Text]
135. Shao SC, Kuo LT, Chien RN, et al. SGLT2 inhibitors in patients with type 2 diabetes with non-alcoholic fatty liver diseases: an umbrella review of systematic reviews. BMJ Open Diabetes Res Care. 2020 Dec;8(2):.[Abstract][Full Text]
136. Clinicaltrials.gov. Comparison of the effects of thiazolidinediones(TZD), sodium-glucose cotransporter 2 inhibitors (SGLT2i) alone and TZD/SGLT2i combination therapy on non-alcoholic fatty liver disease in type 2 diabetic patients with fatty liver. Oct 2020 [internet publication].[Full Text]
137. Clinicaltrials.gov. Effect of empagliflozin on liver fat in non-diabetic patients. Apr 2021 [internet publication].[Full Text]
138. Zein CO, Yerian LM, Gogate P, et al. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011 Nov;54(5):1610-9.[Abstract][Full Text]
139. Van Wagner LB, Koppe SW, Brunt EM, et al. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol. 2011 Jul-Sep;10(3):277-86.[Abstract][Full Text]
140. Zein CO, Lopez R, Fu X, et al. Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. Hepatology. 2012 Oct;56(4):1291-9.[Abstract][Full Text]
141. 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 Feb 13;387(10019):679-90.[Abstract]
142. ClinicalTrials.gov. Efficacy and safety of pemvidutide in subjects with nonalcoholic steatohepatitis (NASH) (IMPACT Trial) (IMPACT). ClinicalTrials.gov Identifier: NCT05989711. May 2024 [internet publication].[Full Text]
143. Romero-Gómez M, Lawitz E, Shankar RR, et al. A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. J Hepatol. 2023 Oct;79(4):888-97.[Abstract][Full Text]
144. ClinicalTrials.gov. A clinical study of efinopegdutide in participants with precirrhotic nonalcoholic steatohepatitis (NASH) (MK-6024-013). ClinicalTrials.gov Identifier: NCT05877547. Jun 2024 [internet publication].[Full Text]
145. Parker HM, Johnson NA, Burdon CA, et al. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012 Apr;56(4):944-51.[Abstract][Full Text]
146. Yu L, Yuan M, Wang L. The effect of omega-3 unsaturated fatty acids on non-alcoholic fatty liver disease: A systematic review and meta-analysis of RCTs. Pak J Med Sci. 2017 Jul-Aug;33(4):1022-8.[Abstract][Full Text]
147. Malaguarnera M, Gargante MP, Volti GG. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis - a randomized and controlled clinical trial. Am J Gastroenterol. 2010 Jun;105(6):1338-45.[Abstract]
148. Safadi R, Konikoff FM, Mahamid M, et al. The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014 Dec;12(12):2085-91;e1.[Abstract][Full Text]
149. Simon TG, Henson J, Osganian S, et al. Daily aspirin use associated with reduced risk for fibrosis progression in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2019 Dec;17(13):2776-84.e4.[Abstract][Full Text]
150. Calle RA, Amin NB, Carvajal-Gonzalez S, et al. ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials. Nat Med. 2021 Oct;27(10):1836-48.[Abstract]
151. ClinicalTrials.gov. Metabolic interventions to resolve non-alcoholic steatohepatitis (NASH) with fibrosis (MIRNA). Jun 2022 [internet publication].[Full Text]
152. Watanabe S, Hashimoto E, Ikejima K, et al; Japanese Society of Gastroenterology; Japan Society of Hepatology. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. J Gastroenterol. 2015 Apr;50(4):364-77.[Abstract][Full Text]
153. Cotrim HP, Parise ER, Figueiredo-Mendes C, et al. Nonalcoholic fatty liver disease Brazilian Society of Hepatology consensus. Arq Gastroenterol. 2016 Apr-Jun;53(2):118-22.[Abstract][Full Text]
154. Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.[Abstract][Full Text]
155. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015 Aug;149(2):389-97;e10.[Abstract][Full Text]
156. Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007 Feb;11(1):1-16;vii.[Abstract]
157. Contos MJ, Cales W, Sterling RK, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 2001 Apr;7(4):363-73.[Abstract][Full Text]
158. Kakar S, Dugum M, Cabello R, et al. Incidence of Recurrent NASH-Related Allograft Cirrhosis. Dig Dis Sci. 2019 May;64(5):1356-63.[Abstract]
159. Blonsky JJ, Harrison SA. Review article: nonalcoholic fatty liver disease and hepatitis C virus - partners in crime. Aliment Pharmacol Ther. 2008 May;27(10):855-65.[Abstract][Full Text]
160. Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987 Jan-Feb;7(1):122-8.[Abstract]
161. D'Amico G, Morabito A, Pagliaro L, et al. Survival and prognostic indicators in compensated and decompensated cirrhosis. Dig Dis Sci. 1986 May;31(5):468-75.[Abstract]
162. Grace ND. Prevention of initial variceal hemorrhage. Gastroenterol Clin North Am. 1992 Mar;21(1):149-61.[Abstract]
163. Graham DY, Smith JL. The course of patients after variceal hemorrhage. Gastroenterology. 1981 Apr;80(4):800-9.[Abstract]
164. Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. 2007 Feb;25(suppl 1):3-9.[Abstract][Full Text]
165. Colombo M, de Franchis R, Del Ninno E, et al. Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med. 1991 Sep 5;325(10):675-80.[Abstract][Full Text]
166. Loomba R, Lim JK, Patton H, et al. AGA Clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review. Gastroenterology. 2020 May;158(6):1822-30.[Abstract][Full Text]
167. Ando Y, Jou JH. Nonalcoholic fatty liver disease and recent guideline updates. Clin Liver Dis (Hoboken). 2021 Jan;17(1):23-8.[Abstract][Full Text]
168. Singal AG, Llovet JM, Yarchoan M, et al. AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023 Dec 1;78(6):1922-65.[Full Text]
169. Gines A, Escorsell A, Gines P, et al. Incidence, predictive factors, and treatment of the hepatorenal syndrome with ascites. Gastroenterology. 1993 Jul;105(1):229-36.[Abstract][Full Text]
170. Rodríguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome - a liver-induced lung vascular disorder. N Engl J Med. 2008 May 29;358(22):2378-87.[Abstract]
171. Grilo-Bensusan I, Pascasio-Acevedo JM. Hepatopulmonary syndrome: what we know and what we would like to know. World J Gastroenterol. 2016 Jul 7;22(25):5728-41.[Abstract][Full Text]
172. Infante-Rivard C, Esnaola S, Villeneuve JP. Clinical and statistical validity of conventional prognostic factors in predicting short-term survival among cirrhotics. Hepatology. 1987 Jul-Aug;7(4):660-4.[Abstract]
173. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008 Jun 15;59(6):762-84.[Abstract][Full Text]
174. Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020 Jun;82(6):1445-86.[Abstract][Full Text]
175. Heimbach J, Kulik LM, Finn R, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018 Jan;67(1):358-80.[Abstract][Full Text]
176. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007 Sep;46(3):922-38.[Abstract][Full Text]
177. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended adult immunization schedule for ages 19 years or older - United States, 2024. Nov 2023 [internet publication].[Full Text]
178. UK Health Security Agency. Immunisation against infectious disease: the green book. Nov 2020 [internet publication].[Full Text]