Highlights
- •Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new entity.
- •MAFLD is highly prevalent among patients with obesity and type 2 diabetes.
- •MAFLD and non-alcoholic fatty liver disease (NAFLD) are not two interchangeable terms.
- •Early identification of MAFLD patients at risk of progression is important.
Abstract
Metabolic-dysfunction associated fatty liver disease (MAFLD) is a newly introduced
entity hoping to more precisely define fatty liver disease. Despite the controversies
surrounding MAFLD, the definition is getting more widely accepted by the global liver-health
community. MAFLD represents a cohort of patients enriched with more advanced liver
disease, cardio-renal and metabolic complications with increased mortality. This review
aims to provide all primary care physicians and diabetologists with a clinical management
update from a non-hepatologist’s perspective, and a summary of important findings
from recent studies to raise disease awareness and highlight the relevance of MAFLD
to their daily clinical practice.
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 accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Primary Care DiabetesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.J. Hepatol. 2020; 73: 202-209
- EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease.J. Hepatol. 2016; 64: 1388-1402
- Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.Hepatology. 2019; 69: 2672-2682
- Comparison of MAFLD and NAFLD diagnostic criteria in real world.Liver Int. 2020; 40: 2082-2089
- Impact of the new definition of metabolic associated fatty liver disease on the epidemiology of the disease.Clin. Gastroenterol. Hepatol. 2021; 19 (2161–2171.e2165)
- Metabolic dysfunction-associated fatty liver disease and incident cardiovascular disease risk: a nationwide cohort study.Clin. Gastroenterol. Hepatol. 2021; 19 (2138–2147.e2110)
- Association of MAFLD with diabetes, chronic kidney disease, and cardiovascular disease: a 4.6-year cohort study in China.J. Clin. Endocrinol. Metab. 2022; 107: 88-97
- An observational data meta-analysis on the differences in prevalence and risk factors between MAFLD vs NAFLD.Clin. Gastroenterol. Hepatol. 2021; (S1542-3565(21)01276-3)
- Estimating global prevalence of metabolic dysfunction-associated fatty liver disease in overweight or obese adults.Clin. Gastroenterol. Hepatol. 2021; (S1542-3565(21)00208-1)
- IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045.Diabetes Res. Clin. Pract. 2021; 109119
- 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
- Liver fibrosis by FibroScan((R)) independently of established cardiovascular risk parameters associates with macrovascular and microvascular complications in patients with type 2 diabetes.Liver Int. 2020; 40: 347-354
- Advanced liver fibrosis is common in patients with type 2 diabetes followed in the outpatient setting: the need for systematic screening.Diabetes Care. 2021; 44: 399-406
- A global survey of physicians knowledge about nonalcoholic fatty liver disease.Clin. Gastroenterol. Hepatol. 2021; (S1542-3565(21)00719-9)
- Advancing the global public health agenda for NAFLD: a consensus statement.Nat. Rev. Gastroenterol. Hepatol. 2021; 19: 60-78
- MAFLD enhances clinical practice for liver disease in the Asia-Pacific region.Clin. Mol. Hepatol. 2021; (Online ahead of print)https://doi.org/10.3350/cmh.2021.0310
- Letter regarding “A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement”.J. Hepatol. 2020; 73: 1573-1574
- MAFLD identifies patients with significant hepatic fibrosis better than NAFLD.Liver Int. 2020; 40: 3018-3030
- Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States.J. Hepatol. 2021; 75: 1284-1291
- Prospective study of outcomes in adults with nonalcoholic fatty liver disease.N. Engl. J. Med. 2021; 385: 1559-1569
- Nonalcoholic fatty liver disease progression rates to cirrhosis and progression of cirrhosis to decompensation and mortality: a real world analysis of Medicare data.Aliment. Pharmacol. Ther. 2020; 51: 1149-1159
- Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts.BMC Med. 2019; 17: 95
- AGA clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review.Gastroenterology. 2020; 158: 1822-1830
- 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; 6: 903-913
- Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis.Gut. 2022; 71: 156-162
- Multiple parallel hits hypothesis in nonalcoholic fatty liver disease: revisited after a decade.Hepatology. 2021; 73: 833-842
- Obesity as the common soil of non-alcoholic fatty liver disease and diabetes: role of adipokines.J. Diabetes Investig. 2013; 4: 413-425
- Adipocyte fatty acid-binding protein, cardiovascular diseases and mortality.Front. Immunol. 2021; 12589206
- Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice.J. Hepatol. 2013; 58: 358-364
- Adipocyte fatty acid binding protein promotes the onset and progression of liver fibrosis via mediating the crosstalk between liver sinusoidal endothelial cells and hepatic stellate cells.Adv. Sci. (Weinh). 2021; 8e2003721
- Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease.Hepatology. 2009; 49: 1926-1934
- Circulating level of FABP4 is an independent predictor of metabolic dysfunction-associated fatty liver disease in middle-aged and elderly individuals.J. Diabetes Investig. 2021; (Online ahead of print)https://doi.org/10.1111/jdi.13735
- Association of adipokines with hepatic steatosis and fibrosis in chronic hepatitis B patients on long-term nucleoside analogue.Liver Int. 2019; 39: 1217-1225
- 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
- Screening for nonalcoholic fatty liver disease in persons with type 2 diabetes in the United States is cost-effective: a comprehensive cost-utility analysis.Gastroenterology. 2020; 159 (1985–1987.e1984)
- 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; 17e1003100
- Moderate alcohol consumption is associated with advanced fibrosis in non-alcoholic fatty liver disease and shows a synergistic effect with type 2 diabetes mellitus.Metabolism. 2021; 115154439
- Clinical care pathway for the risk stratification and management of patients with nonalcoholic fatty liver disease.Gastroenterology. 2021; 161: 1657-1669
- Glycemic control predicts severity of hepatocyte ballooning and hepatic fibrosis in nonalcoholic fatty liver disease.Hepatology. 2021; 74: 1220-1233
- Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up.Hepatology. 2015; 61: 1547-1554
- 4. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes—2022.Diabetes Care. 2022; 45: S46-S59
- Non-invasive tests for liver fibrosis in NAFLD: creating pathways between primary healthcare and liver clinics.Liver Int. 2020; 40 Suppl 1: 77-81
- Nonalcoholic fatty liver disease screening in type 2 diabetes mellitus patients in the primary care setting.Hepatol. Commun. 2021; 5: 158-167
- FIB-4 cut-off of 1.3 may be inappropriate in a primary care referral pathway for patients with non-alcoholic fatty liver disease.J. Hepatol. 2020; 73: 216-217
- Clinical utility of noninvasive scores in assessing advanced hepatic fibrosis in patients with type 2 diabetes mellitus: a study in biopsy-proven non-alcoholic fatty liver disease.Acta Diabetol. 2020; 57: 613-618
- Performance of plasma biomarkers and diagnostic panels for nonalcoholic steatohepatitis and advanced fibrosis in patients with type 2 diabetes.Diabetes Care. 2020; 43: 290-297
- 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
- Diabetes liver fibrosis score to detect advanced fibrosis in diabetics with nonalcoholic fatty liver disease.Clin. Gastroenterol. Hepatol. 2021; (S1542-3565(21)00012-4)
- Development of a non-invasive liver fibrosis score based on transient elastography for risk stratification in patients with type 2 diabetes.Endocrinol. Metab. (Seoul). 2021; 36: 134-145
- Association of liver fibrosis with cardiovascular diseases in the general population: the multi-ethnic study of atherosclerosis (MESA).Circ. Cardiovasc. Imaging. 2018; 11e007241
- Liver stiffness severity is associated with increased cardiovascular risk in patients with type 2 diabetes.Clin. Gastroenterol. Hepatol. 2020; 18 (744–746.e741)
- Advanced liver fibrosis measured by transient elastography predicts chronic kidney disease development in individuals with non-alcoholic fatty liver disease.Diabetologia. 2021; (Online ahead of print)https://doi.org/10.1007/s00125-021-05627-9
- Treatment of NAFLD with diet, physical activity and exercise.J. Hepatol. 2017; 67: 829-846
- Insulin resistance is related with liver fibrosis in type 2 diabetic patients with non-alcoholic fatty liver disease proven biopsy and Mediterranean diet pattern as a protective factor.Endocrine. 2020; 68: 557-563
- Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis.JAMA Intern. Med. 2017; 177: 633-640
- Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial.Ann. Intern. Med. 2016; 165: 305-315
- Response to pioglitazone in patients with nonalcoholic steatohepatitis with vs without type 2 diabetes.Clin. Gastroenterol. Hepatol. 2018; 16 (558–566.e552)
- Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors.Nat. Rev. Gastroenterol. Hepatol. 2021; 18: 24-39
- Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study.Lancet. 2016; 387: 679-690
- A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.N. Engl. J. Med. 2021; 384: 1113-1124
- The emerging role of glucagon-like Peptide-1 receptor agonists for the management of NAFLD.J. Clin. Endocrinol. Metab. 2022; 107: 29-38
- Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with non-alcoholic steatohepatitis: PIVENS trial design.Contemp. Clin. Trials. 2009; 30: 88-96
- Role of vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: a randomized controlled trial.Diabetes Care. 2019; 42: 1481-1488
- Sodium-glucose co-transporter 2 inhibitors in nonalcoholic fatty liver disease.Eur. J. Pharmacol. 2021; 907174272
- Effects of sodium-glucose cotransporter 2 inhibitors on non-alcoholic fatty liver disease in patients with type 2 diabetes: a meta-analysis of randomized controlled trials.J. Diabetes Investig. 2020; 11: 1238-1247
- Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease.Diabetes Obes. Metab. 2019; 21: 285-292
- SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.Lancet. 2019; 393: 31-39
- Empagliflozin for the treatment of nonalcoholic steatohepatitis in patients with type 2 diabetes mellitus.Dig. Dis. Sci. 2020; 65: 623-631
- Therapeutic pipeline in nonalcoholic steatohepatitis.Nat. Rev. Gastroenterol. Hepatol. 2021; 18: 373-392
- Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes.Diabetes Care. 2020; 43: 1352-1355
- Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes: a 54-week randomized phase 2b study.Diabetes Care. 2021; 44: 1433-1442
- Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride.J. Hepatol. 2010; 53: 934-940
- Fibroblast growth factor 21 as an emerging metabolic regulator: clinical perspectives.Clin. Endocrinol. (Oxf.). 2013; 78: 489-496
- Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial.Nat. Med. 2021; 27: 1262-1271
- LLF580, an FGF21 analog, reduces triglycerides and hepatic fat in obese adults with modest hypertriglyceridemia.J. Clin. Endocrinol. Metab. 2022; 107: e57-e70
- Non-alcoholic fatty liver disease, metabolic goal achievement with incident cardiovascular disease and eGFR-based chronic kidney disease in patients with prediabetes and diabetes.Metabolism. 2021; 124154874
- On the proposed definition of metabolic-associated fatty liver disease.Clin. Gastroenterol. Hepatol. 2021; 19: 865-870
- Redefining fatty liver disease: an international patient perspective.Lancet Gastroenterol. Hepatol. 2021; 6: 73-79
- The Latin American Association for the Study of the Liver (ALEH) position statement on the redefinition of fatty liver disease.Lancet Gastroenterol. Hepatol. 2021; 6: 65-72
- The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.J. Hepatol. 2021; 75: 454-461
Article info
Publication history
Published online: January 24, 2022
Accepted:
January 20,
2022
Received in revised form:
January 18,
2022
Received:
January 8,
2022
Identification
Copyright
© 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
