Metabolic syndrome and non-alcoholic fatty liver disease
Authors:
Marek Rác; Ubomír Skladaný
Authors‘ workplace:
Interná klinika, Fakultná nemocnica Nitra
Published in:
Forum Diab 2023; 12(2): 68-74
Category:
Overview
Non-alcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of the metabolic syndrome. The epidemiology mirrors the prevalence of obesity and DM2T. It represents the most common chronic liver disease. NAFLD is a general term that encompasses all grades and stages of the disease and refers to a population in which ≥ 5% of hepatocytes exhibit macrovesicular steatosis in the absence of a readily identified alternative cause of steatosis. Globally, the prevalence of NAFLD and NASH is increasing in parallel with the increase in the prevalence of diabetes and obesity. In the adult population, it is estimated to be 30%; the prevalence in the diabetic cohort is virtually ubiquitous. Fibrosis and the presence of steatohepatitis are the primary predictors of disease progression. Fibrosis progression is influenced by many factors such as the presence and severity of metabolic comorbidities, genomic profile and environmental factors. Cardiovascular events and nonhepatic neoplasia are the most common causes of mortality in NAFLD patients without advanced fibrosis; hepatic mortality predominates in patients with advanced fibrosis. The pathogenetic foundation is an imbalance between nutrient supply with inefficient utilization in conjunction with adipose tissue dysfunction. Systemic inflammation, stemming from dysfunctional adipose tissue, contributes to disease progression. Insulin resistance perpetuates the development of NAFLD and, in NASH, promotes disease progression. Patients with NAFLD should be screened for the presence of DM2T and vice versa. Patients with diabetes have a higher risk of NASH and advanced fibrosis, so noninvasive staging of fibrosis is an implicit imperative. Weight reduction improves hepatic steatosis, NASH, and liver fibrosis in a dose-dependent manner. Comprehensive treatment of metabolic comorbidities is best achieved using a multidisciplinary approach and interdisciplinary collaboration.
Keywords:
Adipose tissue – metabolic syndrome – non-alcoholic fatty liver disease – insulin resistance – diabetes mellitus – non-alcoholic steatohepatitis – systemic inflammation
Sources
1. 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. Dostupné z DOI: <http://doi:10.1016/j.jhep.2020.03.039>.
2. Younossi Z, Tacke F, Arrese M et al. Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology 2019; 69(6): 2672–2682. Dostupné z DOI: <https://
3. doi:10.1002/hep.30251>.
4. Sørensen HT, Mellemkjær L, Jepsen P et al. Risk of Cancer in Patients Hospitalized With Fatty Liver: A Danish Cohort Study. J Clin Gastroenterol 2003; 36(4): 356–359. Dostupné z DOI: <https://doi:10.1097/00004836–200304000–00015>.
5. Chalasani N, Younossi Z, Lavine JE et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55(6): 2005–2023. Dostupné z DOI: <https://doi:10.1002/hep.25762>.
6. 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; 77(5): 1797–1835. Dostupné z DOI: <https://doi: 10.1097/HEP.0000000000000323>.
7. Stefan N, Cusi K. A global view of the interplay between non-alcoholic fatty liver disease and diabetes. Lancet Diabetes Endocrinol 2022; 10(4): 284–296. Dostupné z DOI: <https://doi.org/10.1016/S2213–8587(22)00003–1>.
8. McCullough AJ. Pathophysiology of Nonalcoholic Steatohepatitis. J Clin Gastroenterol 2006; 40(Suppl 1): S17-S29. Dostupné z DOI: <https://doi:10.1097/01.mcg.0000168645.86658.22>.
9. Bhala N, Angulo P, van der Poorten D et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011; 54(4): 1208–1216. Dostupné z DOI: <https://doi:10.1002/hep.24491>.
10. Taylor RS, Taylor RJ, Bayliss S et al. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020; 158(6): 1611–1625: e12. Dostupné z DOI: <https://doi:10.1053/j.gastro.2020.01.043>.
11. Valenti L, Romeo S, Nobili V, et al. Destined to develop NAFLD? The predictors of fatty liver from birth to adulthood. J Hepatol 2016; 65(4): 1218–1229. Dostupné z DOI: <https://doi:10.1016/j.jhep.2016.06.010>.
12. Liu Y-L, Patman GL, Leathart JBS et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 2014; 61(1): 75–81. Dostupné z DOI: <https://doi:10.1016/j.jhep.2014.02.030>.
13. Bugianesi E, Gastaldelli A, Vanni E et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 2005; 48(4): 634–642. Dostupné z DOI: <https://doi:10.1007/s00125–005–1682-x>.
14. McPherson S, Hardy T, Henderson E et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: Implications for prognosis and clinical management. J Hepatol 2015; 62(5): 1148–1155. Dostupné z DOI: <https://doi:10.1016/j.jhep.2014.11.034>.
15. Ekstedt M, Franzén LE, Mathiesen UL et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44(4): 865–873. Dostupné z DOI: <https://doi:10.1002/hep.21327>.
16. Younossi ZM, 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(4): 793–801. Dostupné z DOI: <https://doi:10.1016/j.jhep.2019.06.021>.
17. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2021; 18(4): 223–238. Dostupné z DOI: <https://doi:10.1038/s41575–020–00381–6>.
18. Castellana M, Donghia R, Guerra V et al. Performance of Fatty Liver Index in Identifying Non-Alcoholic Fatty Liver Disease in Population Studies. A Meta-Analysis. J Clin Med 2021; 10(9): 1877. Dostupné z DOI: <https://doi:10.3390/jcm10091877>.
19. 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; 385(17): 1559–1569. Dostupné z DOI: <https://doi:10.1056/NEJMoa2029349>.
20. Treeprasertsuk S, Björnsson E, Enders F et al. NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol 2013; 19(8): 1219–1229. Dostupné z DOI: <https://doi:10.3748/wjg.v19.i8.1219>.
21. Vallet-Pichard A, Mallet V, Nalpas B et al. FIB-4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 2007; 46(1): 32–36. Dostupné z DOI: <https://doi:10.1002/hep.21669>.
22. Cao Y, Xiang L, Qi F, Zhang Y, Chen Y, Zhou X. Accuracy of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) for assessing steatosis and fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. eClinicalMedicine 2022; 51. Dostupné z DOI: <https://doi:10.1016/j.eclinm.2022.101547>.
23. 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(2): 367–378. e5. Dostupné z DOI: <https://doi:10.1053/j.gastro.2015.04.005>.
24. Lassailly G, Caiazzo R, Ntandja-Wandji L-C et al. Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis. Gastroenterology 2020; 159(4): 1290–1301 .e5. Dostupné z DOI: <https://doi:10.1053/j.gastro.2020.06.006>.
25. Jiao Y, Lu Y, Li X. Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis. Acta Pharmacol Sin 2015; 36(1): 44–50. Dostupné z DOI: <https://doi:10.1038/aps.2014.116>.
26. Neuschwander-Tetri BA, Loomba R, Sanyal AJ et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 2015; 385(9972): 956–965. Dostupné z DOI: <https://doi:10.1016/S0140–6736(14)61933–4>.
27. Harrison SA, Bashir MR, Guy CD et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2019; 394(10213): 2012–2024. Dostupné z DOI: <https://doi:10.1016/S0140–6736(19)32517–6>.
28. Newsome PN, Buchholtz K, Cusi K et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2020; 384(12): 1113–1124. Dostupné z DOI: <https://doi:10.1056/NEJMoa2028395>.
29. Ratziu V, Harrison SA, Francque S et al. Elafibranor, an Agonist of the Peroxisome Proliferator−Activated Receptor−α and −δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology 2016; 150(5): 1147–1159. e5. Dostupné z DOI: <https://doi:10.1053/j.gastro.2016.01.038>.
30. Tillman EJ, Rolph T. FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases. Front Endocrinol 2020; 11. Dostupné z WWW: <https://www.frontiersin.org/articles/10.3389/fendo.2020.601290>.
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Diabetology Endocrinology Internal medicineArticle was published in
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