Non-alcoholic fatty liver disease: from understanding risk factors to finding optimal treatment regimens: A review

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is now a major risk factor for death among patients with liver disease. Currently, drugs that primarily affect surrogate markers of NAFLD are available. However, none of these drugs showed a significant effect on the course of steatohepatitis and fibrogenesis. The search for the most relevant lifestyle modification programs is still a priority in comprehensive treatment. A clinical case of follow-up of a comorbid patient is presented. Despite comprehensive treatment, disease regression was not achieved. NAFLD therapy remains a relevant issue. Finding new ways to affect the NAFLD course and individualize treatment approaches is necessary.

About the authors

Daria A. Teplyuk

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: teplyouk@gmail.com
ORCID iD: 0000-0002-7628-8851

Assistant

Russian Federation, Moscow

Aliya A. Kaisina

Asfendiyarov Kazakh National Medical University

Email: teplyouk@gmail.com
ORCID iD: 0009-0008-6250-1448

Doctoral Student

Kazakhstan, Almaty

Shabnam I. Ibragimova

Sechenov First Moscow State Medical University (Sechenov University)

Email: teplyouk@gmail.com
ORCID iD: 0000-0002-9509-2643

Graduate Student

Russian Federation, Moscow

Afina A. Bestavashvili

Sechenov First Moscow State Medical University (Sechenov University)

Email: teplyouk@gmail.com
ORCID iD: 0000-0001-7551-1268

Res. Officer

Russian Federation, Moscow

Irina O. Tinkova

Botkin State Clinical Hospital

Email: teplyouk@gmail.com
ORCID iD: 0000-0002-6960-1184

Pathologist

Russian Federation, Moscow

Evgeniia Iu. Pashkova

Botkin State Clinical Hospital

Email: teplyouk@gmail.com
ORCID iD: 0000-0003-1949-914X

Cand. Sci. (Med.)

Russian Federation, Moscow

Jamilya A. Kaibullayeva

Asfendiyarov Kazakh National Medical University

Email: teplyouk@gmail.com
ORCID iD: 0000-0002-0783-4441

Cand. Sci. (Med.)

Kazakhstan, Almaty

Alexander V. Nersesov

Asfendiyarov Kazakh National Medical University

Email: teplyouk@gmail.com
ORCID iD: 0000-0002-8601-3966

D. Sci. (Med.), Prof.

Kazakhstan, Almaty

Chavdar S. Pavlov

Sechenov First Moscow State Medical University (Sechenov University)

Email: teplyouk@gmail.com
ORCID iD: 0000-0001-5031-9798

D. Sci. (Med.), Prof.

Russian Federation, Moscow

References

  1. Riazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7:851-61. doi: 10.1016/S2468-1253(22)00165-0
  2. Valencia-Rodríguez A, Vera-Barajas A, Chávez-Tapia NC, et al. Looking into a new era for the approach of metabolic (dysfunction) associated fatty liver disease. Ann Hepatol. 2020;19:227-9. doi: 10.1016/j.aohep.2020.04.001
  3. López-Velázquez JA, Silva-Vidal KV, Ponciano-Rodríguez G, et al. The prevalence of nonalcoholic fatty liver disease in the Americas. Ann Hepatol. 2014;13:166-78. doi: 10.1016/s1665-2681(19)30879-8
  4. Perumpail BJ, Khan MA, Yoo ER, et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23:8263-76. doi: 10.3748/wjg.v23.i47.8263
  5. Maurice J, Manousou P. Non-alcoholic fatty liver disease. Clin Med. 2018;18:245-50. doi: 10.7861/clinmedicine.18-3-245
  6. Mendez-Sanchez N, Arrese M, Gadano A, et al. 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. doi: 10.1016/S2468-1253(20)30340-X
  7. Younossi Z, Tacke F, Arrese M, et al. Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology. 2019;69:2672-82. doi: 10.1002/hep.30251
  8. Torres DM, Williams CD, Harrison SA. Features, Diagnosis, and Treatment of Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2012;10:837-58. doi: 10.1016/j.cgh.2012.03.011
  9. Nasr P, Ignatova S, Kechagias S, Ekstedt M. Natural history of nonalcoholic fatty liver disease: A prospective follow-up study with serial biopsies. Hepatol Commun. 2018;2:199-210. doi: 10.1002/hep4.1134
  10. Leung C, Yeoh SW, Patrick D, et al. Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease. World J Gastroenterol. 2015;21:1189-96. doi: 10.3748/wjg.v21.i4.1189
  11. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology. 2010;52:1836-46. doi: 10.1002/hep.24001
  12. Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, et al. Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study. Gastroenterology. 2018;155:443-57.e17. doi: 10.1053/j.gastro.2018.04.034
  13. Ballestri S, Zona S, Targher G, et al. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016;31:936-44. doi: 10.1111/jgh.13264
  14. 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
  15. Masarone M, Rosato V, Aglitti A, et al. Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage. PLoS One. 2017;12:1-10. doi: 10.1371/journal.pone.0178473
  16. Haffner SM. Pre-diabetes, insulin resistance, inflammation and CVD risk. Diabetes Res Clin Pract. 2003;61 Suppl. 1:S9-18. doi: 10.1016/s0168-8227(03)00122-0
  17. Sasso FC, Pafundi PC, Marfella R, et al. Adiponectin and insulin resistance are related to restenosis and overall new PCI in subjects with normal glucose tolerance: The prospective AIRE Study. Cardiovasc Diabetol. 2019;18:1-13. doi: 10.1186/s12933-019-0826-0
  18. Stols-Gonçalves D, Hovingh GK, Nieuwdorp M, Holleboom AG. NAFLD and Atherosclerosis: Two Sides of the Same Dysmetabolic Coin? Trends Endocrinol Metab. 2019;30:891-902. doi: 10.1016/j.tem.2019.08.008
  19. Targher G, Lonardo A, Byrne CD. Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol. 2018;14:99-114. doi: 10.1038/nrendo.2017.173
  20. Alexander M, Loomis AK, Fairburn-Beech J, et al. Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease. BMC Med. 2018;16:1-11. doi: 10.1186/s12916-018-1103-x
  21. Charoenngam N, Holick MF. Immunologic effects of vitamin d on human health and disease. Nutrients. 2020;12:1-28. doi: 10.3390/nu12072097
  22. Eslam M, Sanyal AJ, George J, et al. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020;158:1999-2014.e1. doi: 10.1053/j.gastro.2019.11.312
  23. 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;73:202-9. doi: 10.1016/j.jhep.2020.03.039
  24. Nseir W, Artul S, Nasrallah N, Mahamid M. The association between primary bacteremia of presumed gastrointestinal origin and nonalcoholic fatty liver disease. Dig Liver Dis. 2016;48:343-4. doi: 10.1016/j.dld.2015.10.004
  25. Boursier J, Mueller O, Barret M, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2016;63:764-75. doi: 10.1002/hep.28356
  26. Saltzman ET, Palacios T, Thomsen M, Vitetta L. Intestinal microbiome shifts, dysbiosis, inflammation, and non-alcoholic fatty liver disease. Front Microbiol. 2018;9:1-11. doi: 10.3389/fmicb.2018.00061
  27. Mendez-Sanchez N, Cruz-Ramon VC, Ramirez-Perez OL, et al. New aspects of lipotoxicity in nonalcoholic steatohepatitis. Int J Mol Sci. 2018;19. doi: 10.3390/ijms19072034
  28. Fedchuk L, Nascimbeni F, Pais R, et al. Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2014;40:1209-22. doi: 10.1111/apt.12963
  29. Marchesini G, Day CP, Dufour JF, et al. 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
  30. Jennison E, Patel J, Scorletti E, Byrne CD. Diagnosis and management of non-alcoholic fatty liver disease. Postgrad Med J. 2019;95:314-22. doi: 10.1136/postgradmedj-2018-136316
  31. Fan JG, Kim SU, Wong VWS. New trends on obesity and NAFLD in Asia. J Hepatol. 2017;67(4):862-73.
  32. Hydes TJ, Summers N, Brown E, et al. Mechanisms, screening modalities and treatment options for individuals with non-alcoholic fatty liver disease and type 2 diabetes. Diabet Med. 2020;37(11):1793-806.
  33. Zhang C, Yang M. Current options and future directions for nafld and nash treatment. Int J Mol Sci. 2021;22. doi: 10.3390/ijms22147571
  34. Trauner M, Fuchs CD. Novel therapeutic targets for cholestatic and fatty liver disease. Gut. 2022;71:194-209. doi: 10.1136/gutjnl-2021-324305
  35. Marchesini G, Day CP, Dufour JF, et al. EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease. Obes Facts. 2016;9:65-90. doi: 10.1159/000443344
  36. Hallsworth K, Thoma C, Hollingsworth KG, et al. Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: A randomized controlled trial. Clin Sci. 2015;129:1097-105. doi: 10.1042/CS20150308
  37. Coppel J, Hennis P, Gilbert-Kawai E, Grocott MPW. The physiological effects of hypobaric hypoxia versus normobaric hypoxia: A systematic review of crossover trials. Extrem Physiol Med. 2015;4. doi: 10.1186/s13728-014-0021-6
  38. Greer SN, Metcalf JL, Wang Y, Ohh M. The updated biology of hypoxia-inducible factor. EMBO J. 2012;31:2448-60. doi: 10.1038/emboj.2012.125
  39. Arkhipenko YV, Sazontova TG, Zhukova AG. Adaptation to periodic hypoxia and hyperoxia improves resistance of membrane structures in heart, liver, and brain. Bull Exp Biol Med. 2005;140:278-81. doi: 10.1007/s10517-005-0466-0
  40. Mallet RT, Manukhina EB, Ruelas SS. Cardioprotection by Intermittent Hypoxia Conditioning: Evidence, Mechanisms and Therapeutic Potential. Anal. Standar Pelayanan Minimal Pada Instal. Rawat Jalan di RSUD Kota Semarang. 2015;3:103-11.
  41. Burtscher J, Maglione V, Di Pardo A, et al. Rationale for hypoxic and chemical conditioning in Huntington’s disease. Int J Mol Sci. 2021;22:1-22. doi: 10.3390/ijms22020582
  42. Burtscher J, Syed MMK, Lashuel HA, Millet GP. Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson’s Disease? Mov Disord. 2021;36:857-61. doi: 10.1002/mds.28544
  43. Camacho-Cardenosa A, Camacho-Cardenosa M, Brooks D, et al. Effects training in hypoxia on cardiometabolic parameters in obese people: A systematic review of randomized controlled trial. Aten Primaria. 2019;51:397-405. doi: 10.1016/j.aprim.2018.03.011
  44. Qin L, Xiang Y, Song Z, et al. Erythropoietin as a possible mechanism for the effects of intermittent hypoxia on bodyweight, serum glucose and leptin in mice. Regul Pept. 2010;165:168-73. doi: 10.1016/j.regpep.2010.07.163
  45. Sazontova TG, Stryapko NV, Arkhipenko YV. Addition of Hyperoxic Component to Adaptation to Hypoxia Prevents Impairments Induced by Low Doses of Toxicants (Free Radical Oxidation and Proteins of HSP Family). Bull Exp Biol Med. 2016;160:304-7. doi: 10.1007/s10517-016-3157-0
  46. He F, Ru X, Wen T. NRF2, a transcription factor for stress response and beyond. Int J Mol Sci. 2020;21:1-23. doi: 10.3390/ijms21134777
  47. Glazachev O, Kopylov P, Susta D, et al. Adaptations following an intermittent hypoxia-hyperoxia training in coronary artery disease patients: a controlled study. Clin Cardiol. 2017;40:370-6. doi: 10.1002/clc.22670
  48. Dudnik E, Zagaynaya E, Glazachev OS, Susta D. Intermittent hypoxia-hyperoxia conditioning improves cardiorespiratory fitness in older comorbid cardiac outpatients without hematological changes: A randomized controlled trial. High Alt Med Biol. 2018;19:339-43. doi: 10.1089/ham.2018.0014
  49. Tuter DS, Kopylov PY, Syrkin AL, et al. Intermittent systemic hypoxic-hyperoxic training for myocardial protection in patients undergoing coronary artery bypass surgery: First results from a single-centre, randomised controlled trial. Open Hear. 2018;5:1-8. doi: 10.1136/openhrt-2018-000891
  50. Buang Y, Wang YM, Cha JY, et al. Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid. Nutrition. 2005;21:867-73. doi: 10.1016/j.nut.2004.11.019
  51. Lee HS, Nam Y, Chung YH, et al. Beneficial effects of phosphatidylcholine on high-fat diet-induced obesity, hyperlipidemia and fatty liver in mice. Life Sci. 2014;118:7-14. doi: 10.1016/j.lfs.2014.09.027
  52. Gundermann KJ, Gundermann S, Drozdzik M, Mohan Prasad VG. Essential phospholipids in fatty liver: A scientific update. Clin Exp Gastroenterol. 2016;9:105-17. doi: 10.2147/CEG.S96362
  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;8:5235-49. doi: 10.12998/wjcc.v8.i21.5235
  54. Maev IV, Samsonov AA, Palgova LK, et al. Effectiveness of phosphatidylcholine in alleviating steatosis in patients with non-alcoholic fatty liver disease and cardiometabolic comorbidities (MANPOWER study). BMJ Open Gastroenterol. 2020;7:1-10. doi: 10.1136/bmjgast-2019-000341
  55. Le P, Chaitoff A, Rothberg MB, et al. Trends in pioglitazone use among U.S. adults with type 2 diabetes and suspected nonalcoholic fatty liver disease. Expert Opin Investig. Drugs. 2020;29:205-8. doi: 10.1080/13543784.2020.1704731
  56. Corey KE, Wilson LA, Altinbas A, et al. Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions: a post-hoc analysis of the PIVENS trial. Aliment Pharmacol Ther. 2019;49:1205-13. doi: 10.1111/apt.15216
  57. Gawrieh S, Wilson LA, Yates KP, et al. Relationship of ELF and PIIINP With Liver Histology and Response to Vitamin E or Pioglitazone in the PIVENS Trial. Hepatol Commun. 2021;5:786-97. doi: 10.1002/hep4.1680
  58. Brunt EM, Kleiner DE, Wilson LA, et al. Improvements in Histologic Features and Diagnosis Associated With Improvement in Fibrosis in Nonalcoholic Steatohepatitis: Results From the Nonalcoholic Steatohepatitis Clinical Research Network Treatment Trials. Hepatology. 2019;70:522-31. doi: 10.1002/hep.30418
  59. Lian J, Fu J. Pioglitazone for NAFLD Patients With Prediabetes or Type 2 Diabetes Mellitus: A Meta-Analysis. Front Endocrinol (Lausanne). 2021;12:1-12. doi: 10.3389/fendo.2021.615409
  60. Ratziu V, Giral P, Jacqueminet S, et al. Rosiglitazone for Nonalcoholic Steatohepatitis: One-Year Results of the Randomized Placebo-Controlled Fatty Liver Improvement With Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology. 2008;135:100-10. doi: 10.1053/j.gastro.2008.03.078
  61. 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;55:2005-23. doi: 10.1002/hep.25762
  62. Gurka MJ, Mack JA, Chi X, DeBoer MD. Use of metabolic syndrome severity to assess treatment with vitamin E and pioglitazone for non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2021;36:249-56. doi: 10.1111/jgh.15131
  63. Bril F, Biernacki DM, Kalavalapalli S, et al. Role of Vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: A randomized controlled trial. Diabetes Care. 2019;42:1481-8. doi: 10.2337/dc19-0167
  64. Singh S, Osna NA, Kharbanda KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review. World J Gastroenterol. 2017;23:6549-70. doi: 10.3748/wjg.v23.i36.6549
  65. 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(10019):679-90. doi: 10.1016/S0140-6736(15)00803-X
  66. Gastaldelli A, Repetto E, Guja C, et al. Exenatide and dapagliflozin combination improves markers of liver steatosis and fibrosis in patients with type 2 diabetes. Diabetes Obes Metab. 2020;22(3):393-403. doi: 10.1111/dom.13907
  67. Liu L, Yan H, Xia M, et al. Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes. Diabetes Metab Res Rev. 2020;36(5):e3292. doi: 10.1002/dmrr.3292
  68. Mantovani A, Petracca G, Beatrice G, et al. Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Metabolites. 2021;11(2):73. doi: 10.3390/metabo11020073
  69. Bray JJH, Foster-Davies H, Salem A, et al. Glucagon-like peptide-1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomised controlled trials. Diabetes Obes Metab. 2021;23(8):1806-22. doi: 10.1111/dom.14399
  70. Vašura A, Blaho M, Dítě P, et al. Adiponektin u nemocných s metabolickým syndromem a chorobami jater, žlučových cest a pankreatu [Adiponectin in patients with metabolic syndrome and diseases of the liver, bile ducts and pancreas (in Polish)]. Vnitr Lek. 2018;63(12):945-4.
  71. Tas E, Bai S, Ou X, et al. Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity. Front Endocrinol (Lausanne). 2020;11:654. doi: 10.3389/fendo.2020.00654
  72. Chellali S, Boudiba A, Griene L, Koceir EA. Interactions incrétines-adipocytokines chez le sujet diabétique de type 2 avec ou sans stéatose hépatique non alcoolique : intérêt du GLP-1 (glucagon-like peptide-1) comme biomarqueur modulateur [Incretins-adipocytokines interactions in type 2 diabetic subjects with or without non-alcoholic fatty liver disease: interest of GLP-1 (glucagon-like peptide-1) as a modulating biomarker (in French)]. Ann Biol Clin (Paris). 2019;77(3):261-71. doi: 10.1684/abc.2019.1436
  73. de Carvalho CP, Marin DM, de Souza AL, et al. GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism. Obes Surg. 2009;19(3):313-20. doi: 10.1007/s11695-008-9678-5
  74. Xiong X, Lu W, Qin X, et al. Downregulation of the GLP-1/CREB/adiponectin pathway is partially responsible for diabetes-induced dysregulated vascular tone and VSMC dysfunction. Biomed Pharmacother. 2020;127:110218. doi: 10.1016/j.biopha.2020.110218
  75. Patel V, Joharapurkar A, Kshirsagar S, et al. Coagonist of GLP-1 and Glucagon Receptor Ameliorates Development of Non-Alcoholic Fatty Liver Disease. Cardiovasc Hematol Agents Med Chem. 2018;16(1):35-43. doi: 10.2174/1871525716666180118152158
  76. Simental-Mendía LE, Sánchez-García A, Linden-Torres E, Simental-Mendía M. Impact of glucagon-like peptide-1 receptor agonists on adiponectin concentrations: A meta-analysis of randomized controlled trials. Br J Clin Pharmacol. 2021;87(11):4140-9. doi: 10.1111/bcp.14855
  77. Scheen AJ. Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020;16(10):556-77. doi: 10.1038/s41574-020-0392-2
  78. Phrueksotsai S, Pinyopornpanish K, Euathrongchit J, et al. The effects of dapagliflozin on hepatic and visceral fat in type 2 diabetes patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2021;36:2952-9. doi: 10.1111/jgh.15580
  79. Ghosh A, Dutta K, Bhatt SP, et al. Dapagliflozin Improves Body Fat Patterning, and Hepatic and Pancreatic Fat in Patients With Type 2 Diabetes in North India. J Clin Endocrinol Metab. 2022;107(6):e2267-75. doi: 10.1210/clinem/dgac138
  80. Kahl S, Gancheva S, Straßburger K, et al. Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial. Diabetes Care. 2020;43(2):298-305. doi: 10.2337/dc19-0641
  81. Aso Y, Kato K, Sakurai S, et al. Impact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease. Int J Clin Pract. 2019;73(5):e13335. doi: 10.1111/ijcp.13335
  82. Sattar N, Fitchett D, Hantel S, et al. Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial. Diabetologia. 2018;61(10):2155-63. doi: 10.1007/s00125-018-4702-3
  83. Akuta N, Kawamura Y, Fujiyama S, et al. SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology. Intern Med. 2020;59(16):1931-7. doi: 10.2169/internalmedicine.4398-19
  84. Wang Y, Xia N. Influence of Sodium-Glucose Cotransporter-2 Inhibitors on Plasma Adiponectin in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Horm Metab Res. 2022;54(12):833-44. doi: 10.1055/a-1897-6121
  85. Xiao MW, Lin SX, Shen ZH, et al. Systematic Review with Meta-Analysis: The Effects of Probiotics in Nonalcoholic Fatty Liver Disease. Gastroenterol Res Pract. 2019;2019:1484598. doi: 10.1155/2019/1484598
  86. Horvath A, Durdevic M, Leber B, et al. Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis. Nutrients. 2020;12(6):1874. doi: 10.3390/nu12061874
  87. Cai GS, Su H, Zhang J. Protective effect of probiotics in patients with non-alcoholic fatty liver disease. Medicine (Baltimore). 2020;99(32):e21464. doi: 10.1097/MD.0000000000021464
  88. Loman BR, Hernández-Saavedra D, An R, Rector RS. Prebiotic and probiotic treatment of nonalcoholic fatty liver disease: a systematic review and meta-analysis. Nutr Rev. 2018;76(11):822-39. doi: 10.1093/nutrit/nuy031
  89. Mei L, Tang Y, Li M, et al. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver. PLoS One. 2015;10(9):e0138078. doi: 10.1371/journal.pone.0138078
  90. Xue L, He J, Gao N, et al. Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia. Sci Rep. 2017;7:45176. doi: 10.1038/srep45176
  91. Jena PK, Sheng L, Li Y, Wan YY. Probiotics VSL#3 Are Effective in Reversing Non-Alcoholic Steatohepatitis in a Mouse Model. Hepatobiliary Surg Nutr. 2020;9:170-82.
  92. Kim DH, Kim H, Jeong D, et al. Kefir alleviates obesity and hepatic steatosis in high-fat diet-fed mice by modulation of gut microbiota and mycobiota: targeted and untargeted community analysis with correlation of biomarkers. J Nutr Biochem. 2017;44:35-43. doi: 10.1016/j.jnutbio.2017.02.014
  93. Loomba R, Seguritan V, Li W, et al. Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017;25(5):1054-62.e5. doi: 10.1016/j.cmet.2017.04.001
  94. Chen Y, Yang F, Lu H, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54(2):562-72. doi: 10.1002/hep.24423
  95. Shen F, Zheng RD, Sun XQ, et al. Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease. Hepatobiliary Pancreat Dis Int. 2017;16(4):375-81. doi: 10.1016/S1499-3872(17)60019-5

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