Advertisement
Review Article| Volume 107, ISSUE 3, P449-463, May 2023

Download started.

Ok

Nonalcoholic Fatty Liver Disease

A Unique Entity or Part of the Metabolic Syndrome or Both
  • Terry Cheuk-Fung Yip
    Affiliations
    Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong

    Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong

    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
    Search for articles by this author
  • Grace Lai-Hung Wong
    Affiliations
    Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong

    Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong

    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
    Search for articles by this author
  • Vincent Wai-Sun Wong
    Affiliations
    Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong

    Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong

    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
    Search for articles by this author
  • George Boon-Bee Goh
    Correspondence
    Corresponding authors. George Boon-Bee Goh, Department of Gastroenterology and Hepatology, Singapore General Hospital, 20 College Road, Academia, Singapore 169856; Wah-Kheong Chan, Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
    Affiliations
    Department of Gastroenterology and Hepatology, Singapore General Hospital, 20 College Road, Academia, Singapore 169856

    Duke-NUS Medical School, Singapore
    Search for articles by this author
  • Wah-Kheong Chan
    Correspondence
    Corresponding authors. George Boon-Bee Goh, Department of Gastroenterology and Hepatology, Singapore General Hospital, 20 College Road, Academia, Singapore 169856; Wah-Kheong Chan, Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
    Affiliations
    Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
    Search for articles by this author
Published:February 20, 2023DOI:https://doi.org/10.1016/j.mcna.2022.12.003

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Medical Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Wong V.W.S.
        • Chan W.K.
        • 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; 33: 70-85
        • Kuchay M.S.
        • Martinez-Montoro J.I.
        • Choudhary N.S.
        • et al.
        Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges.
        Biomedicines. 2021; 9: 1346
        • Le M.H.
        • Yeo Y.H.
        • Li X.
        • et al.
        2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis.
        Clin Gastroenterol Hepatol. 2021; 20 (e28): 2809-2817
        • Singh S.
        • Allen A.M.
        • 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 (e1-9; [quiz: e39-40]): 643-654
        • Dulai P.S.
        • Singh S.
        • Patel J.
        • et al.
        Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis.
        Hepatology. 2017; 65: 1557-1565
        • Huang D.Q.
        • El-Serag H.B.
        • Loomba R.
        Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention.
        Nat Rev Gastroenterol Hepatol. 2021; 18: 223-238
        • Wong R.J.
        • 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: 547-555
        • Wong R.J.
        • Cheung R.
        • Ahmed A.
        Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.
        Hepatology. 2014; 59: 2188-2195
        • National Cholesterol Education Program
        Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Alberti K.G.
        • Zimmet P.
        • Shaw J.
        • et al.
        The metabolic syndrome--a new worldwide definition.
        Lancet. 2005; 366: 1059-1062
        • Sarafidis P.A.
        • Nilsson P.M.
        The metabolic syndrome: a glance at its history.
        J Hypertens. 2006; 24: 621-626
        • Alberti K.G.
        • Zimmet P.Z.
        Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.
        Diabet Med. 1998; 15: 539-553
        • Balkau B.
        • Charles M.A.
        Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR).
        Diabet Med. 1999; 16: 442-443
        • Chan W.K.
        • Wong V.W.
        Meaning of non-overlapping patients between the MAFLD and NAFLD definitions.
        Liver Int. 2022; 42: 271-273
        • Eslam M.
        • Newsome P.N.
        • Sarin S.K.
        • et al.
        A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement.
        J Hepatol. 2020; 73: 202-209
        • Wong V.W.
        • Hui A.Y.
        • Tsang S.W.
        • et al.
        Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease.
        Aliment Pharmacol Ther. 2006; 24: 1215-1222
        • Younossi Z.M.
        • Golabi P.
        • de Avila L.
        • et al.
        The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis.
        J Hepatol. 2019; 71: 793-801
        • Mantovani A.
        • Petracca G.
        • Beatrice G.
        • et al.
        Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals.
        Gut. 2021; 70: 962-969
        • Kwok R.
        • Choi K.C.
        • Wong G.L.
        • et al.
        Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study.
        Gut. 2016; 65: 1359-1368
        • Lee H.W.
        • Wong G.L.
        • Kwok R.
        • et al.
        Serial Transient Elastography Examinations to Monitor Patients With Type 2 Diabetes: A Prospective Cohort Study.
        Hepatology. 2020; 72: 1230-1241
        • Calzadilla-Bertot L.
        • Vilar-Gomez E.
        • Wong V.W.
        • et al.
        ABIDE: An Accurate Predictive Model of Liver Decompensation in Patients With Nonalcoholic Fatty Liver-Related Cirrhosis.
        Hepatology. 2021; 73: 2238-2250
        • Zhang X.
        • Wong G.L.
        • Yip T.C.
        • et al.
        Risk of liver-related events by age and diabetes duration in patients with diabetes and nonalcoholic fatty liver disease.
        Hepatology. 2022; 76: 1409-1422
        • Targher G.
        • Corey K.E.
        • Byrne C.D.
        • et al.
        The complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments.
        Nat Rev Gastroenterol Hepatol. 2021; 18: 599-612
        • Younossi Z.M.
        • Koenig A.B.
        • Abdelatif D.
        • et al.
        Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.
        Hepatology. 2016; 64: 73-84
        • Polyzos S.A.
        • Kountouras J.
        • Mantzoros C.S.
        Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics.
        Metabolism. 2019; 92: 82-97
        • Li L.
        • Liu D.W.
        • Yan H.Y.
        • et al.
        Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies.
        Obes Rev. 2016; 17: 510-519
        • Smith G.I.
        • Mittendorfer B.
        • Klein S.
        Metabolically healthy obesity: facts and fantasies.
        J Clin Invest. 2019; 129: 3978-3989
        • Cho I.Y.
        • Chang Y.
        • Sung E.
        • et al.
        Weight Change and the Development of Nonalcoholic Fatty Liver Disease in Metabolically Healthy Overweight Individuals.
        Clin Gastroenterol Hepatol. 2022; 20: e583-e599
        • Lonardo A.
        • Mantovani A.
        • Lugari S.
        • et al.
        Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity.
        Ann Hepatol. 2020; 19: 359-366
        • Sookoian S.
        • Pirola C.J.
        Systematic review with meta-analysis: the significance of histological disease severity in lean patients with nonalcoholic fatty liver disease.
        Aliment Pharmacol Ther. 2018; 47: 16-25
        • Fassio E.
        • Alvarez E.
        • Dominguez N.
        • et al.
        Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies.
        Hepatology. 2004; 40: 820-826
        • Jarvis H.
        • Craig D.
        • Barker R.
        • et al.
        Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies.
        Plos Med. 2020; 17: e1003100
        • Polyzos S.A.
        • Kountouras J.
        • Mantzoros C.S.
        Adipokines in nonalcoholic fatty liver disease.
        Metabolism. 2016; 65: 1062-1079
        • Zhao Y.C.
        • Zhao G.J.
        • Chen Z.
        • et al.
        Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension.
        Hypertension. 2020; 75: 275-284
        • Oikonomou D.
        • Georgiopoulos G.
        • Katsi V.
        • et al.
        Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated?.
        Eur J Gastroenterol Hepatol. 2018; 30: 979-985
        • Wu S.
        • Wu F.
        • Ding Y.
        • et al.
        Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis.
        Sci Rep. 2016; 6: 33386
        • Stranges S.
        • Trevisan M.
        • Dorn J.M.
        • et al.
        Body fat distribution, liver enzymes, and risk of hypertension: evidence from the Western New York Study.
        Hypertension. 2005; 46: 1186-1193
        • Bonnet F.
        • Gastaldelli A.
        • Pihan-Le Bars F.
        • et al.
        Gamma-glutamyltransferase, fatty liver index and hepatic insulin resistance are associated with incident hypertension in two longitudinal studies.
        J Hypertens. 2017; 35: 493-500
        • Lau K.
        • Lorbeer R.
        • Haring R.
        • et al.
        The association between fatty liver disease and blood pressure in a population-based prospective longitudinal study.
        J Hypertens. 2010; 28: 1829-1835
        • Ryoo J.H.
        • Suh Y.J.
        • Shin H.C.
        • et al.
        Clinical association between non-alcoholic fatty liver disease and the development of hypertension.
        J Gastroenterol Hepatol. 2014; 29: 1926-1931
        • Zhang T.
        • Zhang C.
        • Zhang Y.
        • et al.
        Metabolic syndrome and its components as predictors of nonalcoholic fatty liver disease in a northern urban Han Chinese population: a prospective cohort study.
        Atherosclerosis. 2015; 240: 144-148
        • Aneni E.C.
        • Oni E.T.
        • Martin S.S.
        • et al.
        Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk.
        J Hypertens. 2015; 33: 1207-1214
        • Sorrentino P.
        • Terracciano L.
        • D'Angelo S.
        • et al.
        Predicting fibrosis worsening in obese patients with NASH through parenchymal fibronectin, HOMA-IR, and hypertension.
        Am J Gastroenterol. 2010; 105: 336-344
        • Ma J.
        • Hwang S.J.
        • Pedley A.
        • et al.
        Bi-directional analysis between fatty liver and cardiovascular disease risk factors.
        J Hepatol. 2017; 66: 390-397
        • Carnagarin R.
        • Matthews V.
        • Zaldivia M.T.K.
        • et al.
        The bidirectional interaction between the sympathetic nervous system and immune mechanisms in the pathogenesis of hypertension.
        Br J Pharmacol. 2019; 176: 1839-1852
        • Satou R.
        • Penrose H.
        • Navar L.G.
        Inflammation as a Regulator of the Renin-Angiotensin System and Blood Pressure.
        Curr Hypertens Rep. 2018; 20: 100
        • Lee H.J.
        • Lee C.H.
        • Kim S.
        • et al.
        Association between vascular inflammation and non-alcoholic fatty liver disease: Analysis by (18)F-fluorodeoxyglucose positron emission tomography.
        Metabolism. 2017; 67: 72-79
        • Younossi Z.M.
        • Ratziu V.
        • Loomba R.
        • et al.
        Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial.
        Lancet. 2019; 394: 2184-2196
        • Amor A.J.
        • Perea V.
        Dyslipidemia in nonalcoholic fatty liver disease.
        Curr Opin Endocrinol Diabetes Obes. 2019; 26: 103-108
        • Chalasani N.
        • Younossi Z.
        • Lavine J.E.
        • 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: 328-357
        • Powell E.E.
        • Wong V.W.
        • Rinella M.
        Non-alcoholic fatty liver disease.
        Lancet. 2021; 397: 2212-2224
        • Ipsen D.H.
        • Lykkesfeldt J.
        • Tveden-Nyborg P.
        Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease.
        Cell Mol Life Sci. 2018; 75: 3313-3327
        • Zewinger S.
        • Reiser J.
        • Jankowski V.
        • et al.
        Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation.
        Nat Immunol. 2020; 21: 30-41
        • Kanwal F.
        • Kramer J.R.
        • Li L.
        • et al.
        Effect of Metabolic Traits on the Risk of Cirrhosis and Hepatocellular Cancer in Nonalcoholic Fatty Liver Disease.
        Hepatology. 2020; 71: 808-819
        • Ng C.H.
        • Wong Z.Y.
        • Chew N.W.S.
        • et al.
        Hypertension is prevalent in non-alcoholic fatty liver disease and increases all-cause and cardiovascular mortality.
        Front Cardiovasc Med. 2022; 9: 942753
        • Pitisuttithum P.
        • Chan W.K.
        • Goh G.B.
        • et al.
        Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease: The Gut and Obesity Asia initiative.
        World J Gastroenterol. 2020; 26: 2416-2426
        • Aminian A.
        • Al-Kurd A.
        • Wilson R.
        • et al.
        Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis.
        JAMA. 2021; 326: 2031-2042
        • Zhou Y.Y.
        • Zhou X.D.
        • Wu S.J.
        • et al.
        Synergistic increase in cardiovascular risk in diabetes mellitus with nonalcoholic fatty liver disease: a meta-analysis.
        Eur J Gastroenterol Hepatol. 2018; 30: 631-636
        • Mantovani A.
        • Petracca G.
        • Beatrice G.
        • et al.
        Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies.
        Gut. 2022; 71: 778-788
        • Chen Z.F.
        • Dong X.L.
        • Huang Q.K.
        • et al.
        The combined effect of non-alcoholic fatty liver disease and metabolic syndrome on colorectal carcinoma mortality: a retrospective in Chinese females.
        World J Surg Oncol. 2018; 16: 163
        • Zhang X.
        • Wong G.L.
        • Yip T.C.
        • et al.
        Angiotensin-converting enzyme inhibitors prevent liver-related events in nonalcoholic fatty liver disease.
        Hepatology. 2022; 76: 469-482
        • Golabi P.
        • Otgonsuren M.
        • de Avila L.
        • et al.
        Components of metabolic syndrome increase the risk of mortality in nonalcoholic fatty liver disease (NAFLD).
        Medicine (Baltimore). 2018; 97: e0214
        • Kim D.
        • Konyn P.
        • Sandhu K.K.
        • et al.
        Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States.
        J Hepatol. 2021; 75: 1284-1291
        • Kanwal F.
        • Shubrook J.H.
        • Adams L.A.
        • et al.
        Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease.
        Gastroenterology. 2021; 161: 1657-1669
        • Vilar-Gomez E.
        • Martinez-Perez Y.
        • Calzadilla-Bertot L.
        • et al.
        Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis.
        Gastroenterology. 2015; 149 (e5; quiz e14-5): 367-378
        • Wong V.W.
        • Chan R.S.
        • Wong G.L.
        • et al.
        Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial.
        J Hepatol. 2013; 59: 536-542
        • Wong V.W.
        • Wong G.L.
        • Chan R.S.
        • et al.
        Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease.
        J Hepatol. 2018; 69: 1349-1356
        • Newsome P.N.
        • Buchholtz K.
        • Cusi K.
        • et al.
        A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis.
        N Engl J Med. 2021; 384: 1113-1124
        • Loomba R.
        • Abdelmalek M.F.
        • Armstrong M.
        • et al.
        Semaglutide 2.4 mg once weekly improved liver and metabolic parameters, and was well tolerated, in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial.
        J Hepatol. 2022; 77: S10
        • Hsiang J.C.
        • Wong V.W.
        SGLT2 Inhibitors in Liver Patients.
        Clin Gastroenterol Hepatol. 2020; 18: 2168-2172 e2
        • Lange N.F.
        • Radu P.
        • Dufour J.F.
        Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention.
        J Hepatol. 2021; 75: 1217-1227
      1. 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: 1388-1402
        • Eslam M.
        • Sarin S.K.
        • Wong V.W.
        • et al.
        The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.
        Hepatol Int. 2020; 14: 889-919