Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD): A General Overview and Approach in Clinical Practice
Main Article Content
Abstract
Metabolic dysfunction associated steatotic liver disease (MASLD) or previously known Non-alcoholic fatty liver disease (NAFLD) is a common condition with an estimated global prevalence of around 30%. It is becoming a public health concern due to its close association with type 2 diabetes mellitus and obesity. It is important to screen for those with inflammation and fibrosis to halt the progression to cirrhosis. Cirrhosis is associated with liver related complications and liver cancer. Currently, there are no targeted treatments for MASLD at this stage and most treatments are currently in clinical trials. The focus of treatment had been on managing underlying risk metabolic risk factors.
The purpose of this review to inform the readers of the change in the nomenclature from NAFLD to MASLD. This review will also focus on the background of MASLD, the pathogenesis as well as assessment and treatment of patients with MASLD.
Keywords:
Non-alcoholic fatty liver disease (NAFLD), Metabolic dysfunction associated steatotic liver disease (MASLD), steatosis, steatohepatitis, fibrosis, cirrhosis
Article Details
How to Cite
THAN, Nwe Ni.
Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD): A General Overview and Approach in Clinical Practice.
Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4610>. Date accessed: 16 may 2024.
doi: https://doi.org/10.18103/mra.v11i11.4610.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Anstee QM, Darlay R, Cockell S, et al. Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort☆. J Hepatol. 2020;73(3):505-515. doi:10.1016/j.jhep.2020.04.003
2. Golabi P, Paik JM, AlQahtani S, Younossi Y, Tuncer G, Younossi ZM. Burden of non-alcoholic fatty liver disease in Asia, the Middle East and North Africa: Data from Global Burden of Disease 2009-2019. J Hepatol. 2021;75(4):795-809. doi:10.1016/j.jhep.2021.05.022
3. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335-1347. doi:10.1097/HEP.0000000000000004
4. Nguyen MH, Le MH, Yeo YH, et al. Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach. Clin Mol Hepatol. 2022;28(4):841-850. doi:10.3350/cmh.2022.0239
5. Younossi ZM, Henry L. Fatty Liver Through the Ages: Nonalcoholic Steatohepatitis. Endocrine Practice. 2022;28(2):204-213. doi:10.1016/j.eprac.2021.12.010
6. Chaudhry A, Noor J, Batool S, Fatima G, Noor R. Advancements in Diagnostic and Therapeutic Interventions of Non-alcoholic Fatty Liver Disease: A Literature Review. Cureus. Published online September 8, 2023. doi:10.7759/cureus.44924
7. Dufour JF, Anstee QM, Bugianesi E, et al. Current therapies and new developments in NASH. Gut. 2022;71(10):2123-2134. doi:10.1136/gutjnl-2021-326874
8. Jayachandran M, Qu S. Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies. Rev Endocr Metab Disord. Published online October 16, 2023. doi:10.1007/s11154-023-09843-z
9. Mijangos-Trejo A, Nuño-Lambarri N, Barbero-Becerra V, Uribe-Esquivel M, Vidal-Cevallos P, Chávez-Tapia N. Prebiotics and Probiotics: Therapeutic Tools for Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2023;24(19):14918. doi:10.3390/ijms241914918
10. Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-209. doi:10.1016/j.jhep.2020.03.039
11. Rinella ME, Lazarus J V., Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. Published online June 2023. doi:10.1016/j.jhep.2023.06.003
12. Dulai PS, 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(5):1557-1565. doi:10.1002/hep.29085
13. Srivastava A, Gailer R, Tanwar S, et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J Hepatol. 2019;71(2):371-378. doi:10.1016/j.jhep.2019.03.033
14. 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;7(8):755-769. doi:10.1016/S2468-1253(22)00061-9
15. Chen J, Hu P, Wang Y, Zhu Z. Association between type 2 diabetes status and prevalence of liver steatosis and fibrosis among adults aged ≥ 40 years. BMC Endocr Disord. 2022;22(1):128. doi:10.1186/s12902-022-01046-y
16. Su Y, Chien K, Yang S, Chia W, Chen J, Chen Y. Nonalcoholic Fatty Liver Disease Is Associated With Decreased Bone Mineral Density in Adults: A Systematic Review and Meta‐Analysis. Journal of Bone and Mineral Research. 2023;38(8):1092-1103. doi:10.1002/jbmr.4862
17. Sumida Y, Yoneda M. Current and future pharmacological therapies for NAFLD/NASH. J Gastroenterol. 2018;53(3):362-376. doi:10.1007/s00535-017-1415-1
18. Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67(4):829-846. doi:10.1016/j.jhep.2017.05.016
19. Verrastro O, Panunzi S, Castagneto-Gissey L, et al. Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial. The Lancet. 2023;401(10390):1786-1797. doi:10.1016/S0140-6736(23)00634-7
20. Ratziu V, Francque S, Sanyal A. Breakthroughs in therapies for NASH and remaining challenges. J Hepatol. 2022;76(6):1263-1278. doi:10.1016/j.jhep.2022.04.002
21. Prikhodko VA, Bezborodkina NN, Okovityi S V. Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. Biomedicines. 2022;10(2). doi:10.3390/biomedicines10020274
22. Prasoppokakorn T, Pitisuttithum P, Treeprasertsuk S. Pharmacological therapeutics: Current trends for metabolic dysfunction-associated fatty liver disease (mafld). J Clin Transl Hepatol. 2021;9(6):939-946. doi:10.14218/JCTH.2021.00189
23. Harrison SA, Loomba R, Dubourg J, Ratziu V, Noureddin M. Clinical Trial Landscape in NASH. Clinical Gastroenterology and Hepatology. 2023;21(8):2001-2014. doi:10.1016/j.cgh.2023.03.041
24. Younossi ZM, 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. The Lancet. 2019;394(10215):2184-2196. doi:10.1016/S0140-6736(19)33041-7
25. Tyagi S, Sharma S, Gupta P, Saini A, Kaushal C. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011;2(4):236. doi:10.4103/2231-4040.90879
26. Lefere S, Puengel T, Hundertmark J, et al. Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages☆. J Hepatol. 2020;73(4):757-770. doi:10.1016/j.jhep.2020.04.025
27. Kaul U, Parmar D, Manjunath K, et al. New dual peroxisome proliferator activated receptor agonist—Saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence. Cardiovasc Diabetol. 2019;18(1):80. doi:10.1186/s12933-019-0884-3
28. 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. The Lancet. 2016;387(10019):679-690. doi:10.1016/S0140-6736(15)00803-X
29. Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. New England Journal of Medicine. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395
30. Loomba R, Abdelmalek MF, Armstrong MJ, et al. Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8(6):511-522. doi:10.1016/S2468-1253(23)00068-7
31. Raza S, Rajak S, Upadhyay A, Tewari A, Sinha RA. Current Treatment Paradigms and Emerging Therapies for NAFLD/NASH.
32. Lee J Il, Lee HW, Lee KS, Lee HS, Park JY. Effects of Statin Use on the Development and Progression of Nonalcoholic Fatty Liver Disease: A Nationwide Nested Case-Control Study. American Journal of Gastroenterology. 2021;116(1):116-124. doi:10.14309/ajg.0000000000000845
33. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58(3):429-442. doi:10.1007/s00125-014-3460-0
34. Portillo-Sanchez P, Cusi K. Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2 Diabetes Mellitus. Clin Diabetes Endocrinol. 2016;2(1):9. doi:10.1186/s40842-016-0027-7
35. Yau H, Rivera K, Lomonaco R, Cusi K. The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus. Curr Diab Rep. 2013;13(3):329-341. doi:10.1007/s11892-013-0378-8
36. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52(1):79-104. doi:10.1002/hep.23623
37. Campbell JE, Drucker DJ. Pharmacology, Physiology, and Mechanisms of Incretin Hormone Action. Cell Metab. 2013;17(6):819-837. doi:10.1016/j.cmet.2013.04.008
38. Dicker D. DPP-4 Inhibitors. Diabetes Care. 2011;34(Supplement_2):S276-S278. doi:10.2337/dc11-s229
2. Golabi P, Paik JM, AlQahtani S, Younossi Y, Tuncer G, Younossi ZM. Burden of non-alcoholic fatty liver disease in Asia, the Middle East and North Africa: Data from Global Burden of Disease 2009-2019. J Hepatol. 2021;75(4):795-809. doi:10.1016/j.jhep.2021.05.022
3. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335-1347. doi:10.1097/HEP.0000000000000004
4. Nguyen MH, Le MH, Yeo YH, et al. Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach. Clin Mol Hepatol. 2022;28(4):841-850. doi:10.3350/cmh.2022.0239
5. Younossi ZM, Henry L. Fatty Liver Through the Ages: Nonalcoholic Steatohepatitis. Endocrine Practice. 2022;28(2):204-213. doi:10.1016/j.eprac.2021.12.010
6. Chaudhry A, Noor J, Batool S, Fatima G, Noor R. Advancements in Diagnostic and Therapeutic Interventions of Non-alcoholic Fatty Liver Disease: A Literature Review. Cureus. Published online September 8, 2023. doi:10.7759/cureus.44924
7. Dufour JF, Anstee QM, Bugianesi E, et al. Current therapies and new developments in NASH. Gut. 2022;71(10):2123-2134. doi:10.1136/gutjnl-2021-326874
8. Jayachandran M, Qu S. Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies. Rev Endocr Metab Disord. Published online October 16, 2023. doi:10.1007/s11154-023-09843-z
9. Mijangos-Trejo A, Nuño-Lambarri N, Barbero-Becerra V, Uribe-Esquivel M, Vidal-Cevallos P, Chávez-Tapia N. Prebiotics and Probiotics: Therapeutic Tools for Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2023;24(19):14918. doi:10.3390/ijms241914918
10. Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-209. doi:10.1016/j.jhep.2020.03.039
11. Rinella ME, Lazarus J V., Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. Published online June 2023. doi:10.1016/j.jhep.2023.06.003
12. Dulai PS, 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(5):1557-1565. doi:10.1002/hep.29085
13. Srivastava A, Gailer R, Tanwar S, et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J Hepatol. 2019;71(2):371-378. doi:10.1016/j.jhep.2019.03.033
14. 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;7(8):755-769. doi:10.1016/S2468-1253(22)00061-9
15. Chen J, Hu P, Wang Y, Zhu Z. Association between type 2 diabetes status and prevalence of liver steatosis and fibrosis among adults aged ≥ 40 years. BMC Endocr Disord. 2022;22(1):128. doi:10.1186/s12902-022-01046-y
16. Su Y, Chien K, Yang S, Chia W, Chen J, Chen Y. Nonalcoholic Fatty Liver Disease Is Associated With Decreased Bone Mineral Density in Adults: A Systematic Review and Meta‐Analysis. Journal of Bone and Mineral Research. 2023;38(8):1092-1103. doi:10.1002/jbmr.4862
17. Sumida Y, Yoneda M. Current and future pharmacological therapies for NAFLD/NASH. J Gastroenterol. 2018;53(3):362-376. doi:10.1007/s00535-017-1415-1
18. Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67(4):829-846. doi:10.1016/j.jhep.2017.05.016
19. Verrastro O, Panunzi S, Castagneto-Gissey L, et al. Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial. The Lancet. 2023;401(10390):1786-1797. doi:10.1016/S0140-6736(23)00634-7
20. Ratziu V, Francque S, Sanyal A. Breakthroughs in therapies for NASH and remaining challenges. J Hepatol. 2022;76(6):1263-1278. doi:10.1016/j.jhep.2022.04.002
21. Prikhodko VA, Bezborodkina NN, Okovityi S V. Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. Biomedicines. 2022;10(2). doi:10.3390/biomedicines10020274
22. Prasoppokakorn T, Pitisuttithum P, Treeprasertsuk S. Pharmacological therapeutics: Current trends for metabolic dysfunction-associated fatty liver disease (mafld). J Clin Transl Hepatol. 2021;9(6):939-946. doi:10.14218/JCTH.2021.00189
23. Harrison SA, Loomba R, Dubourg J, Ratziu V, Noureddin M. Clinical Trial Landscape in NASH. Clinical Gastroenterology and Hepatology. 2023;21(8):2001-2014. doi:10.1016/j.cgh.2023.03.041
24. Younossi ZM, 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. The Lancet. 2019;394(10215):2184-2196. doi:10.1016/S0140-6736(19)33041-7
25. Tyagi S, Sharma S, Gupta P, Saini A, Kaushal C. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011;2(4):236. doi:10.4103/2231-4040.90879
26. Lefere S, Puengel T, Hundertmark J, et al. Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages☆. J Hepatol. 2020;73(4):757-770. doi:10.1016/j.jhep.2020.04.025
27. Kaul U, Parmar D, Manjunath K, et al. New dual peroxisome proliferator activated receptor agonist—Saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence. Cardiovasc Diabetol. 2019;18(1):80. doi:10.1186/s12933-019-0884-3
28. 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. The Lancet. 2016;387(10019):679-690. doi:10.1016/S0140-6736(15)00803-X
29. Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. New England Journal of Medicine. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395
30. Loomba R, Abdelmalek MF, Armstrong MJ, et al. Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8(6):511-522. doi:10.1016/S2468-1253(23)00068-7
31. Raza S, Rajak S, Upadhyay A, Tewari A, Sinha RA. Current Treatment Paradigms and Emerging Therapies for NAFLD/NASH.
32. Lee J Il, Lee HW, Lee KS, Lee HS, Park JY. Effects of Statin Use on the Development and Progression of Nonalcoholic Fatty Liver Disease: A Nationwide Nested Case-Control Study. American Journal of Gastroenterology. 2021;116(1):116-124. doi:10.14309/ajg.0000000000000845
33. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58(3):429-442. doi:10.1007/s00125-014-3460-0
34. Portillo-Sanchez P, Cusi K. Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2 Diabetes Mellitus. Clin Diabetes Endocrinol. 2016;2(1):9. doi:10.1186/s40842-016-0027-7
35. Yau H, Rivera K, Lomonaco R, Cusi K. The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus. Curr Diab Rep. 2013;13(3):329-341. doi:10.1007/s11892-013-0378-8
36. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52(1):79-104. doi:10.1002/hep.23623
37. Campbell JE, Drucker DJ. Pharmacology, Physiology, and Mechanisms of Incretin Hormone Action. Cell Metab. 2013;17(6):819-837. doi:10.1016/j.cmet.2013.04.008
38. Dicker D. DPP-4 Inhibitors. Diabetes Care. 2011;34(Supplement_2):S276-S278. doi:10.2337/dc11-s229