Non-alcoholic fatty liver disease: aspects of management of a comorbid patient. A review

Cover Page

Cite item

Full Text

Abstract

Against the background of the rapid increase in the prevalence of obesity worldwide, the frequency of the development of metabolic disorders associated with it is increasing. Non-alcoholic fatty liver disease (NAFLD) is recognized as the main hepatic manifestation of metabolic syndrome. Currently, NAFLD affects about 25–30% of the world's population and, in most cases, is associated with obesity and type 2 diabetes, as well as with increased cardiovascular risk. Diagnosis of NAFLD includes laboratory and instrumental research methods, various non-invasive tests, and the “gold standard” for confirming the diagnosis is a liver biopsy. Due to the greater availability and sufficient information content, ultrasound methods of research come to the fore in the examination of patients at risk. Lifestyle modification remains the cornerstone in the management of such patients, however, given the complex pathogenesis of the disease, treatment of NAFLD may include several therapeutic strategies. In the treatment of comorbid patients, some groups of hypoglycemic drugs are used, including ar-GLP-1, i-NGL-2, pioglitazone, lipid-lowering drugs, drugs for the treatment of obesity. The so-called hepatoprotectors, including essential phospholipids (EFL), have demonstrated their effectiveness in reducing liver damage due to antioxidant, antifibrotic, and lipid-regulating effects. According to a number of studies, EFL helps to reduce the severity of steatosis, improving both objective and subjective manifestations of hepatic dysfunction. In this connection, the guidelines of various countries include EFL group drugs in the protocol of treatment of patients with NAFLD both in monotherapy and in combination with other drugs.

About the authors

Tatiana Y. Demidova

Pirogov Russian National Research Medical University

Email: fati_2526@mail.ru
ORCID iD: 0000-0001-6385-540X

д-р мед. наук, проф., зав. каф. эндокринологии лечебного фак-та

Russian Federation, Moscow

Fatima O. Ushanova

Pirogov Russian National Research Medical University

Author for correspondence.
Email: fati_2526@mail.ru
ORCID iD: 0000-0001-5512-6899

канд. мед. наук, ассистент каф. эндокринологии лечебного фак-та

Russian Federation, Moscow

References

  1. Kleiner DE, Makhlouf HR. Histology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in Adults and Children. Clin Liver Dis. 2016;20(2):293-312. doi: 10.1016/j.cld.2015.10.011
  2. 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;64:73-84. doi: 10.1002/hep.28431
  3. Tilg H, Moschen AR, Roden M. NAFLD and diabetes mellitus. Nat Rev Gastroenterol Hepatol. 2017;14:32-42. doi: 10.1038/nrgastro.2016.147
  4. Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11-20. doi: 10.1038/nrgastro.2017.109
  5. Huber Y, Schulz A, Schmidtmann I, et al. Prevalence and risk factors of advanced liver fibrosis in a population-based study in Germany. Hepatol Commun. 2022;6:1457-66. doi: 10.1002/hep4.1899
  6. Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;141:1249-53. doi: 10.1053/j.gastro.2011.06.061
  7. Kelly T, Yang W, Chen CS, et al. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008;32(9):1431-7. doi: 10.1038/ijo.2008.102
  8. Zhou YY, Zhou XD, Wu SJ, et al. Nonalcoholic fatty liver disease contributes to subclinical atherosclerosis: a systematic review and meta-analysis. Hepatol Commun. 2018;2(4):376-92. doi: 10.1002/hep4.1155
  9. Targher G, Byrne CD, Lonardo A, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol. 2016;65(3):589-600. DOI:10.1016/ j.jhep.2016.05.013
  10. Golabi P, Paik JM, Eberly K, et al. Causes of death in patients with non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease and chronic viral hepatitis B and C. Ann Hepatol. 2022;27:100556. doi: 10.1016/j.aohep.2021.100556
  11. Simon TG, Roelstraete B, Khalili H, et al. Mortality in biopsyconfirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut. 2021;70:1375-82. doi: 10.1136/gutjnl-2020-322786
  12. Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020;158(7):1999-2014.e1. doi: 10.1053/j.gastro.2019.11.312
  13. Younossi ZM, Rinella ME, Sanyal AJ, et al. From NAFLD to MAFLD: implications of a premature change in terminology. Hepatology. 2021;73:1194-8. doi: 10.1002/hep.31420
  14. Grander С, Grabherr F, Tilg H. Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options. Cardiovasc Res. 2023;119(9):1787-98. doi: 10.1093/cvr/cvad095
  15. Duan Y, Pan X, Luo J, et al. Association of inflammatory cytokines with non-alcoholic fatty liver disease. Front Immunol. 2022;13:880298. doi: 10.3389/fimmu.2022.880298
  16. Samuel VT, Liu ZX, Qu X, et al. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem. 2004;279:32345-53. doi: 10.1074/jbc.M313478200
  17. Aron-Wisnewsky J, Vigliotti C, Witjes J, et al. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Nat Rev Gastroenterol Hepatol. 2020;17:279-97. doi: 10.1038/s41575-020-0269-9
  18. Alferink LJM, Radjabzadeh D, Erler NS, et al. Metagenomics P. And hepatic steatosis in a population-based study of 1,355 adults. Hepatology. 2021;73:968-82. doi: 10.1002/hep.31417
  19. Lee G, You HJ, Bajaj JS, et al. Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD. Nat Commun. 2020;11:4982. doi: 10.1038/s41467-020-18754-5
  20. Parthasarathy G, Revelo X, Malhi H. Pathogenesis of Nonalcoholic Steatohepatitis: An Overview. Hepatol Communications. 2020;4(4):478-92. doi: 10.1002/hep4.1479
  21. Haas JT, Francque S, Staels B. Pathophysiology and mechanisms of nonalcoholic fatty liver disease. Annu Rev Physiol. 2016;78:181-205. doi: 10.1146/annurev-physiol021115-105331
  22. Chalasani N, Younossi Z, Lavine JE, 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(1):328-57. doi: 10.1002/hep.29367
  23. Bril F, Ortiz-Lopez C, Lomonaco R, et al. Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver Internat. 2015;35:2139-46. doi: 10.1111/liv.12840
  24. Xiao G, Zhu S, Xiao X, et al. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: a meta-analysis. Hepatology. 2017;66:1486-501. doi: 10.1002/hep.29302
  25. Mózes FE, Lee JA, Selvaraj EA, et al. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut. 2022;71:1006-19. doi: 10.1136/gutjnl-2021-324243
  26. 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;75(3):659-89. doi: 10.1016/j.jhep.2021.05.025
  27. 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;64:1388-402. doi: 10.1016/j.jhep.2015.11.004
  28. Ginès P, Castera L, Lammert F, et al. Population screening for liver fibrosis: toward early diagnosis and intervention for chronic liver diseases. Hepatology. 2022;75:219-28. doi: 10.1002/hep.32163
  29. Howard BV, Wylie-Rosett J. Sugar and cardiovascular disease: a statement for healthcare professionals from the committee on nutrition of the council on nutrition, physical activity, and metabolism of the American Heart Association. Circulation. 2002;106:523-7. doi: 10.1161/01.cir.0000019552.77778.04
  30. Gerber L, Otgonsuren M, Mishra A, et al. Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study. Aliment Pharmacol Ther. 2012;36:772-81. doi: 10.1111/apt.12038
  31. Cusi K, Orsak B, Bril F, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes Mellitus: a randomized trial. Ann Int Med. 2016;165:305-15. doi: 10.7326/M15-1774
  32. Kumar J, Memon RS, Shahid I, et al. Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review, meta-analysis and evidence map. Dig Liver Dis. 2021;53(1):44-51. doi: 10.1016/j.dld.2020.08.021
  33. Kuchay MS, Krishan S, Mishra SK, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT trial). Diabetes Care. 2018;41:1801-8. doi: 10.2337/dc18-0165
  34. Mantovani A, Byrne CD, Scorletti E, et al. Efficacy and safety of antihyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: an updated systematic review of randomized controlled trials. Diabetes Metab. 2020;46:427-41. doi: 10.1016/j.diabet.2019
  35. 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;387:679-90. doi: 10.1016/S0140-6736(15)00803-X
  36. Newsome PN, Buchholtz K, Cusi K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24. doi: 10.1056/NEJMoa2028395
  37. Дедов И.И., Мокрышева Н.Г., Мельниченко Г.А., и др. Ожирение. Клинические рекомендации. Consilium Medicum. 2021;23(4):311-25 [Dedov II, Mokrysheva NG, Mel’nichenko GA, et al. Obesity. Clinical guidelines. Consilium Medicum. 2021;23(4):311-25 (in Russian)]. doi: 10.26442/20751753.2021.4.200832
  38. Chauhan M, Singh K, Thuluvath PJ. Bariatric surgery in NAFLD. Dig Dis Sci. 2022;67:408-22. doi: 10.1007/s10620-021-07317-3
  39. Lassailly G, Caiazzo R, Ntandja-Wandji LC, et al. Bariatric surgery provides long-term resolution of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology. 2020;159:1290-301. doi: 10.1053/j.gastro.2020.06.006
  40. Simon TG, Duberg AS, Aleman S, et al. Lipophilic statins and risk for hepatocellular carcinoma and death in patients with chronic viral hepatitis: results from a Nationwide Swedish Population. Ann Intern Med. 2019;171(5):318-27. doi: 10.7326/M18-2753
  41. Ивашкин В.Т., Маевская М.В., Жаркова М.С., и др. Клинические рекомендации Российского общества по изучению печени, Российской гастроэнтерологической ассоциации, Российской ассоциации эндокринологов, Российской ассоциации геронтологов и гериатров и Национального общества профилактической кардиологии по диагностике и лечению неалкогольной жировой болезни печени. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2022;32(4):104-40 [Ivashkin VT, Maevskaya MV, Zharkova MS, et al. Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(4):104-40 (in Russian)]. doi: 10.22416/1382-4376-2022-32-4-104-140
  42. Rinella ME, Dufour JF, Anstee QM, et al. Non-invasive evaluation of response to obeticholic acid in patients with NASH: results from the REGENERATE study. J Hepatol. 2022;76:536-48. doi: 10.1016/j.jhep.2021.10.029
  43. Ando Y, Jou JH. Nonalcoholic Fatty Liver Disease and Recent Guideline Updates. Clin Liver Dis (Hoboken). 2021;17(1):23-8. doi: 10.1002/cld.1045
  44. Лазебник Л.Б., Голованова Е.В., Туркина С.В., и др. Неалкогольная жировая болезнь печени у взрослых: клиника, диагностика, лечение. Рекомендации для терапевтов, третья версия. Экспериментальная и клиническая гастроэнтерология. 2021;1(1):4-52 [Lazebnik LB, Golovanova EV, Turkina SV, et al. Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021;1(1):4-52 (in Russian)]. doi: 10.31146/1682-8658-ecg-185-1-4-52
  45. Miller ER, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37-46. doi: 10.7326/0003-4819-142-1-200501040-00110
  46. Abner EL, Schmitt FA, Mendiondo MS, et al. Vitamin E and all- cause mortality: a meta-analysis. Curr Aging Sci. 2011;4(2):158-70. doi: 10.2174/1874609811104020158
  47. Gundermann KJ, Gundermann S, Drozdzik M, Mohan Prasad VG. Essential phospholipids in fatty liver: a scien-tific update. Clin Exp Gastroenterol. 2016;9:105-17. doi: 10.2147/CEG.S96362
  48. Sas E, Grinevich V, Efimov O, Shcherbina N. Beneficial influence of polyunsaturated phosphatidylcholine enhances functional liver condition and liver structure in patients with nonalcoholic steatohepatitis accompanied by diabetes type 2. Results of prolonged randomized blinded prospective clinical study [abstract]. J Hepatol. 2013;58:S549.
  49. Zhiguo L. Efficacy of polyene phosphatidylcholine in combination with metformin for diabetes complicated with non-alcoholic fatty liver disease. Inner Mongol Journal of Traditional Chinese Medicine. 2013;31:10-1.
  50. Dajani AI, Abu Hammour AM, Zakaria MA, et al. Essential phospholipids as a supportive adjunct in the management of patients with NAFLD. Arab J Gastroenterol. 2015;16(3-4):99-104. doi: 10.1016/j.ajg.2015.09.001
  51. Ivashkin VT, Maevskaya MV, Shirokova EN, et al. Correlation of Objective Endpoints and Subjective Patient-Reported Outcomes in NAFLD Treatment with Essential Phospholipids: Real-World Data Based on Pooled Analysis of Observational Studies. Drugs Real World Outcomes. 2021;8(3):369-82. doi: 10.1007/s40801-021-00250-x
  52. Yin D, Kong L. Observation for curative effect of Essentiale in treatment of fatty liver caused by diabetes mellitus. Med J Q Ilu. 2000;15:277-8.
  53. Dajani AI, Popovic B. Essential phospholipids for nonalcoholic fatty liver disease associated with metabolic syndrome: A systematic review and network meta-analysis. World J Clin Cases. 2020;8(21):5235-49. doi: 10.12998/wjcc.v8.i21.5235
  54. Maev IV, Samsonov AA, Palgova LK, et al. Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia. BMJ Open Gastroenterol. 2019;18;6(1):e000307. doi: 10.1136/bmjgast-2019-00030
  55. Manzillo G, Piccinino F, Surrenti C, et al. Multicentre Double-Blind Placebo-Controlled Study of Intravenous and Oral S-Adenosyl-LMethionine (SAMe) in Cholestatic Patients with Liver Disease. Drug Invest. 1994;24:90-100. doi: 10.1007/BF03258369
  56. Shankar R, Virukalpattigopalratham MP, Singh T. Heptral (Ademetionine) in intrahepatic cholestasis due to chronic non-alcoholic liver disease: subgroup analysis of results of a multicentre observational study in India. J Clin Experim Hepatol. 2014;4(S2):s30-8.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Multifactorial pathogenesis of non-alcoholic fatty liver disease (adapted [14]).

Download (391KB)
3. Fig. 2. General principles of multifactorial treatment of non-alcoholic fatty liver disease.

Download (110KB)

Copyright (c) 2023 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies