Clinical Practice Guidelines for Adult MASLD in Bosnia and Herzegovina: National Recommendations for Diagnosis, Risk Stratification, and Treatment
DOI:
https://doi.org/10.5644/ama2006-124.515Keywords:
MASLD, Clinical Guidelines, Management, Bosnia and HerzegovinaAbstract
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in Bosnia and Herzegovina and a major contributor to liver- and cardiovascular-related morbidity and mortality. These national guidelines provide the first country-specific, evidence-based recommendations for the diagnosis, risk stratification, and management of MASLD, covering the full disease spectrum from steatosis to cirrhosis and its complications. MASLD management is based on a coordinated, stepwise model across primary, secondary, and tertiary healthcare levels, with primary healthcare serving as the central gatekeeper and coordinator of care. Active case-finding of clinically significant fibrosis is emphasized, particularly in high-risk populations, such as individuals with type 2 diabetes mellitus or obesity. Primary healthcare plays a key role in early risk assessment through systematic evaluation of metabolic risk factors and first-line use of simple non-invasive tools, notably the FIB-4 index. A stepwise non-invasive diagnostic algorithm is recommended, with elastography (preferably vibration-con- trolled transient elastography or 2D shear wave elastography where available) used for further assessment in patients with in- determinate or high-risk results. Lifestyle modification and optimal management of cardiometabolic comorbidities remain the foundations of MASLD treatment. In eligible patients with type 2 diabetes mellitus and/or overweight or obesity, glucagon-like peptide-1 receptor agonists may be considered, while bariatric surgery represents an option for selected individuals with persistent obesity. Advanced MASLD, including cirrhosis, requires multidisciplinary management, surveillance for hepatocellular carcinoma, and evaluation for liver transplantation in cases of decompensation. These guidelines aim to standardize MASLD care in Bosnia and Herzegovina and strengthen the pivotal role of primary healthcare within the national MASLD care pathway.
References
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 on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031. PMID: 38851997.
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-835. doi: 10.1097/HEP.0000000000000323. PMID: 36727674.
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):1335-47. doi: 10.1097/HEP.0000000000000004. PMID: 36626630.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. doi: 10.1002/hep.28431. PMID: 26707365.
Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, Caballeria J, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol. 2018;69(4):896-904. doi: 10.1016/j.jhep.2018.05.036. PMID: 29886156.
Mantovani A, Zaza G, Byrne CD, Lonardo A, Zoppini G, Bonora E, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism. 2018;79:64-76. doi: 10.1016/j.metabol.2017.11.003. PMID: 29137912.
Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and metaanalysis. Hepatology. 2017;65(5):1557-65. doi: 10.1002/hep.29085. PMID: 28130788.
Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-54. doi: 10.1002/hep.27368. PMID: 25125077.
Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-9. doi: 10.1016/j.jhep.2020.03.039. PMID: 32278004.
Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908-22. doi: 10.1038/s41591-018-0104-9. PMID: 29967350.
Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40(12):1461-5. doi: 10.1038/ng.257. PMID: 18820647.
Lonardo A, Nascimbeni F, Ballestri S, Fairweather D, Win S, Than TA, et al. Sex Differences in Nonalcoholic Fatty Liver Disease: State of the Art and Identification of Research Gaps. Hepatology. 2019;70(4):1457-69. doi: 10.1002/hep.30626. PMID: 30924946.
Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, 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. doi: 10.1016/j.jhep.2019.06.021. PMID: 31279902.
Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, 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. PMID: 26608256.
da Silva Pereira ENG, Franco RLC, Santos RDCD, Daliry A. Statins and non-alcoholic fatty liver disease: A concise review. Biomed Pharmacother. 2025;183:117805. doi: 10.1016/j.biopha.2024.117805. PMID: 39755024.
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. doi: 10.1093/eurheartj/ehy339. PMID: 30165516.
Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, et al. Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients. Gastroenterology. 2015;149(2):379-88; quiz e15-6. doi: 10.1053/j.gastro.2015.04.014. PMID: 25917783.
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, 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. PMID: 28714183.
Paul S, Davis AM. Diagnosis and Management of Nonalcoholic Fatty Liver Disease. JAMA. 2018;320(23):2474-5. doi: 10.1001/jama.2018.17365. PMID: 30476962.
Başaranoğlu M, Örmeci N. Nonalcoholic fatty liver disease: diagnosis, pathogenesis, and management. Turk J Gastroenterol. 2014;25(2):127-32. doi: 10.5152/tjg.2014.7675. PMID: 25003670.
Younossi ZM, Golabi P, Price JK, Owrangi S, Gundu-Rao N, Satchi R, et al. The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes. Clin Gastroenterol Hepatol. 2024;22(10):1999-2010.e8. doi: 10.1016/j.cgh.2024.03.006. PMID: 38521116.
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. PMID: 34166721.
van Kleef LA, Sonneveld MJ, de Man RA, de Knegt RJ. Poor performance of FIB-4 in elderly individuals at risk for chronic liver disease - implications for the clinical utility of the EASL NIT guideline. J Hepatol. 2022;76(1):245-6. doi: 10.1016/j.jhep.2021.08.017. PMID: 34461208.
Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a metaanalysis. Hepatology. 2011;54(3):1082-90. doi: 10.1002/hep.24452. PMID: 21618575.
Caussy C, Johansson L. Magnetic resonance-based biomarkers in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Endocrinol Diabetes Metab. 2020;3(4):e00134. doi: 10.1002/edm2.134. PMID:
33102797.
Singh S, Venkatesh SK, Loomba R, Wang Z, Sirlin C, Chen J, et al. Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled analysis. Eur Radiol. 2016;26(5):1431-40. doi: 10.1007/s00330-015-3949-z. PMID: 26314479.
Newsome PN, Sasso M, Deeks JJ, Paredes A, Boursier J, Chan WK, et al. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. 2020;5(4):362-73. doi: 10.1016/S2468-1253(19)30383-8. PMID: 32027858.
Ravaioli F, Dajti E, Mantovani A, Newsome PN, Targher G, Colecchia A. Diagnostic accuracy of FibroScan-AST (FAST) score for the non-invasive identification of patients with fibrotic non-alcoholic steatohepatitis: a systematic review and meta-analysis. Gut. 2023;72(7):1399-409. doi: 10.1136/gutjnl-2022-328689. PMID: 36599683.
Natarajan Y, Loomba R. Magnetic Resonance Elastography for the Clinical Risk Assessment of Fibrosis, Cirrhosis, and Portal Hypertension in Patients With NAFLD. J Clin Exp Hepatol. 2022;12(1):174-9. doi: 10.1016/j.jceh.2021.08.002. PMID: 35068797.
Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-54. doi: 10.1002/hep.21496. PMID: 17393509.
31. McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265-9. doi: 10.1136/gut.2010.216077. PMID: 20801772.
McPherson S, Anstee QM, Henderson E, Day CP, Burt AD. Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels? Eur J Gastroenterol Hepatol. 2013;25(6):652-8. doi: 10.1097/MEG.0b013e32835d72cf. PMID: 23325287.
Demir M, Lang S, Nierhoff D, Drebber U, Hardt A, Wedemeyer I, et al. Stepwise combination of simple noninvasive fibrosis scoring systems increases diagnostic accuracy in nonalcoholic fatty liver disease. J
Clin Gastroenterol. 2013;47(8):719-26. doi: 10.1097/MCG.0b013e3182819a89. PMID: 23442837.
Alkhouri N, Sedki E, Alisi A, Lopez R, Pinzani M, Feldstein AE, et al. Combined pediatric NAFLD fibrosis index and transient elastography to predict clinically significant fibrosis in children with fatty liver disease. Liver Int. 2013;33(1):79-85. doi: 10.1111/liv.12024. PMID: 23146095.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82(2):315-74. doi: 10.1016/j.jhep.2024.08.028. PMID: 39690085.
Linero PL, Castilla-Guerra L. Management of Cardiovascular Risk in the Non-alcoholic Fatty Liver Disease Setting. Eur Cardiol. 2024;19:e02. doi: 10.15420/ecr.2023.19. PMCID: PMC11131151.
Duell PB, Welty FK, Miller M, Chait A, Hammond G, Ahmad Z, et al. Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arterioscler
Thromb Vasc Biol. 2022;42(6):e168-85. doi: 10.1161/ATV.0000000000000153. PMID: 35418240.
Saavedra R, Ramirez B, Jay B. Strategies to Manage Obesity: Lifestyle. Methodist Debakey Cardiovasc J. 2025;21(2):53-61. doi: 10.14797/mdcvj.1510. PMID: 39990756.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015;149(2):367-78.e5; quiz e14-5. doi: 10.1053/j.gastro.2015.04.005. PMID: 25865049.
Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67(4):829-46. doi: 10.1016/j.jhep.2017.05.016. PMID: 28545937.
Stavropoulos K, Imprialos K, Pittaras A, Faselis C, Narayan P, Kokkinos P. Lifestyle Modifications in Non-Alcoholic Fatty Liver Disease and Non- Alcoholic Steatohepatitis. Curr Vasc Pharmacol. 2018;16(3):239-45. doi: 10.2174/1570161115666170621080835. PMID: 28637408.
Lassailly G, Caiazzo R, Ntandja-Wandji LC, Gnemmi V, Baud G, Verkindt H, et al. Bariatric Surgery Provides Longterm Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis. Gastroenterology. 2020;159(4):1290-301.e5. doi: 10.1053/j.gastro.2020.06.006. PMID: 32553765.
Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018;378(25):e34. doi: 10.1056/NEJMoa1800389. PMID: 29897866.
Nseir W, Hellou E, Assy N. Role of diet and lifestyle changes in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(28):9338-44. doi: 10.3748/wjg.v20. i28.9338. PMID: 25071328.
Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;57(1):157-66. doi: 10.1016/j.jhep.2012.02.023. PMID: 22414768.
Hallsworth K, Fattakhova G, Hollingsworth KG, Thoma C, Moore S, Taylor R, et al. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut. 2011;60(9):1278-83. doi: 10.1136/gut.2011.242073. PMID: 21708823.
Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009;50(4):1105-12. doi: 10.1002/hep.23129. PMID: 19637289.
Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ. 2017;359:j5024. doi: 10.1136/bmj.j5024. PMID: 29167102.
Kennedy OJ, Roderick P, Poole R, Parkes J. Coffee, caffeine and non-alcoholic fatty liver disease? Therap Adv Gastroenterol. 2016;9(3):417-8. doi: 10.1177/1756283X16636765. PMID: 27134669.
Jung HS, Chang Y, Kwon MJ, Sung E, Yun KE, Cho YK, et al. Smoking and the Risk of Non-Alcoholic Fatty Liver Disease: A Cohort Study. Am J Gastroenterol. 2019;114(3):453-63. doi: 10.1038/s41395-018-0283-5.
PMID: 30353055.
Kim NH, Jung YS, Hong HP, Park JH, Kim HJ, Park DI, et al. Association between cotinine-verified smoking status and risk of nonalcoholic fatty liver disease. Liver Int. 2018; 38(8):1487-94. doi: 10.1111/liv.13701. PMID: 29359396.
Kasper P, Martin A, Lang S, Kütting F, Goeser T, Demir M, et al. NAFLD and cardiovascular diseases: a clinical review. Clin Res Cardiol. 2021;110(7):921-37. doi: 10.1007/s00392-020-01709-7. PMID: 32696080.
Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K, et al. Safety and efficacy of longterm statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet. 2010;376(9756):1916-22. doi: 10.1016/S0140-6736(10)61272-X. PMID: 21109302.
Alkasabrah O, Joshi DK, Hafeez A, Agrawal SP, Frishman WH, Aronow WS. Statins and the Cardio-Hepatic Axis: Balancing Cardiovascular Protection with Liver Disease Safety. Cardiol Rev. 2025 Nov 8. doi: 10.1097/CRD.0000000000001122. PMID: 41204625.
Abdulrazzak E, Fakhoury B, Jaan A, Ebrahim M, Alabdul Razzak I, Shehadah A, et al. Statin Therapy and Portal Pressure Reduction in Cirrhosis: A Systematic Review and Meta-Analysis. Liver Int. 2025;45(10):e70326. doi: 10.1111/liv.70326. PMID: 40891266.
Haukeland JW, Konopski Z, Eggesbø HB, von Volkmann HL, Raschpichler G, Bjøro K, et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009;44(7):853-60. doi: 10.1080/00365520902845268. PMID: 19811343.
Rouabhia S, Milic N, Abenavoli L. Metformin in the treatment of non-alcoholic fatty liver disease: safety, efficacy and mechanism. Expert Rev Gastroenterol Hepatol. 2014;8(4):343-9. doi: 10.1586/17474124.2014.894880. PMID: 24580044.
Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021;384(12):1113-24. doi: 10.1056/NEJMoa2028395. PMID: 33185364.
Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, 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. PMID: 26608256.
Borodavkin P, Sheridan W, Coelho C, Oštarijaš E, Zaïr ZM, Miras AD, et al. Effects of glucagon-like peptide-1 receptor agonists on histopathological and secondary biomarkers of non-alcoholic steatohepatitis: A systematic review and meta-analysis. Diabetes Obes Metab. 2022;24(2):337-42. doi: 10.1111/dom.14565. PMID: 34605124.
Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir JS, 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(8):1801-8. doi: 10.2337/dc18-0165. PMID: 29895557.
Sattar N, Fitchett D, Hantel S, George JT, Zinman B. 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. PMID: 30066148.
Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci. 2008;65:2461-83. doi: 10.1007/s00018-008-7568-6. PMID: 18488143.
Amaral JD, Viana RJ, Ramalho RM, Steer CJ, Rodrigues CM. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res. 2009;50:1721-34. doi: 10.1194/jlr.R900011-JLR200. PMID: 19417220.
65. Zerem E, Kunosic S, Kurtcehajic A, Zerem D, Zerem O. Bile acids in metabolic dysfunction-associated steatotic liver disease. World J Hepatol. 2025;17(8):108606. doi: 10.4254/wjh.v17.i8.108606. PMID: 40901599.
Simental-Mendía M, Sánchez-García A, Simental- Mendía LE. Effect of ursodeoxycholic acid on liver markers: A systematic review and meta-analysis of randomized placebo-controlled clinical trials. Br J Clin Pharmacol. 2020;86:1476-88. doi: 10.1111/bcp.14311. PMID: 32285958.
Lin X, Mai M, He T, Huang H, Zhang P, Xia E, et al. Efficiency of ursodeoxycholic acid for the treatment of nonalcoholic steatohepatitis: A systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol.
2022;16:537-45. doi: 10.1080/17474124.2022.2083605. PMID: 35617696.
Ratziu V, de Ledinghen V, Oberti F, Mathurin P, Wartelle-Bladou C, Renou C, et al. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011;54:1011-9. doi: 10.1016/j.jhep.2010.08.030. PMID: 21145828.
69. Zhang W, Tang Y, Huang J, Hu H. Efficacy of ursodeoxycholic acid in nonalcoholic fatty liver disease: An updated meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2020;29(4):696-705. doi: 10.6133/apjcn.202012_29(4).0004. PMID: 33377363.
Leuschner UF, Lindenthal B, Herrmann G, Arnold JC, Rössle M, Cordes HJ, et al. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a doubleblind, randomized, placebo-controlled trial. Hepatology.2010;52(2):472-9. doi: 10.1002/hep.23727. PMID: 20683947.
Neuman MG, Malnick S, Chertin L. Gamma glutamyl transferase - an underestimated marker for cardiovascular disease and the metabolic syndrome. J Pharm Pharm Sci. 2020;23(1):65-74. doi: 10.18433/jpps30923. PMID: 32310756.
Zhao Y, Xin X, Luo XP. The relationship between the ratio of gamma-glutamyltransferase to high-density lipoprotein cholesterol and the risk of diabetes mellitus using publicly available data: a secondary analysis based on a longitudinal study in Japan. Lipids Health Dis. 2023;22(1):7. doi: 10.1186/s12944-023-01772-9. PMID: 36650520.
Nadinskaia M, Maevskaya M, Ivashkin V, Kodzoeva K, Pirogova I, Chesnokov E, et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(10):959-75. doi: 10.3748/wjg.v27.i10.959. PMID: 33776366.
Ko WK, Lee SH, Kim SJ, Jo MJ, Kumar H, Han IB, et al. Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages. PLoS One.
2017;12(6):e0180673. doi: 10.1371/journal.pone.0180673. PMID: 28665991.
Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675-85. doi: 10.1056/NEJMoa0907929. PMID: 20427778.
Juraschek SP, Col H, Ferro K, Turkson-Ocran RN, Cluett JL, Davis RB, et al. DASH-Patterned Groceries and Effects on Blood Pressure: The GoFresh Randomized Clinical Trial. JAMA. 2026;335(1):36-48. doi: 10.1001/
jama.2025.21112. PMID: 41206973.
Pietu F, Guillaud O, Walter T, Vallin M, Hervieu V, Scoazec JY, et al. Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: long-term results. Clin Res Hepatol Gastroenterol. 2012;36(2):146-55. doi: 10.1016/j.clinre.2011.10.011. PMID: 22154224.
Dufour JF, Oneta CM, Gonvers JJ, Bihl F, Cerny A, Cereda JM, et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4(12):1537-43. doi: 10.1016/j.cgh.2006.09.025. PMID: 17162245.
Ersöz G, Günşar F, Karasu Z, Akay S, Batur Y, Akarca US. Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment. Turk J Gastroenterol. 2005;16(3):124-8. PMID: 16245220.
Barchetta I, Angelico F, Del Ben M, Baroni MG, Pozzilli P, Morini S, et al. Strong association between nonalcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med. 2011;9:85. doi: 10.1186/1741-7015-9-85. PMID: 21749681.
Kitson MT, Roberts SK. D-livering the message: the importance of vitamin D status in chronic liver disease. J Hepatol. 2012;57(4):897-909. doi: 10.1016/j.jhep.2012.04.033. PMID: 22634121.
Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509. doi: 10.1056/NEJMoa2309000. PMID: 38324483.
Hashim HT, Alhatemi AQM, Riaz S, Al-Ghuraibawi MA, Alabide AS, Saeed H, et al. Unveiling Resmetirom: A systematic review and meta-analysis on its impact on liver function and safety in non-alcoholic steatohepatitis treatment. JGH Open. 2024;8(10):e70025. doi: 10.1002/jgh3.70025. PMID: 39359614.
Raja A, Subhash Sagar R, Saeed S, Zia Ul Haq A, Khan O, Dileep Bhimani P, et al. Safety and efficacy of resmetirom in the treatment of patients with non-alcoholic steatohepatitis and liver fibrosis: a systematic review and metaanalysis. Ann Med Surg (Lond). 2024;86(7):4130-8. doi: 10.1097/MS9.0000000000002195. PMID: 38989228.
Knezović E, Hefer M, Blažanović S, Petrović A, Tomičić V, Srb N, et al. Drug Pipeline for MASLD: What Can Be Learned from the Successful Story of Resmetirom. Curr Issues Mol Biol. 2025;47(3):154. doi: 10.3390/
cimb47030154. PMID: 40136408.
Au K, Zheng MH, Lee WJ, Ghanem OM, Mahawar K, Shabbir A, et al. Resmetirom and Metabolic Dysfunction-Associated Steatohepatitis: Perspectives on Multidisciplinary Management from Global Healthcare Professionals. Curr Obes Rep. 2024;13(4):818-30. doi: 10.1007/s13679-024-00582-z. PMID: 39110384.
Wahlström A, Sayin SI, Marschall HU, Bäckhed F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016;24:41-50. doi: 10.1016/j.cmet.2016.05.005. PMID: 27320064.
Beuers U, Trauner M, Jansen P, Poupon R. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol. 2015;62: S25-S37. doi: 10.1016/j.jhep.2015.02.023. PMID: 25920087.
Wang J, Gao J, Zhang Q, Lu J, Yang Y, Cai X, et al. Ileal FXR Knockdown Ameliorates MASLD Progression in Rats via Modulating Bile Acid Metabolism Mediated by Gut Microbiota. J Gastroenterol Hepatol. 2025;40(8):2091-103. doi: 10.1111/jgh.17017. PMID: 40411313.
Rodrigues CM, Steer CJ. The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent. Expert Opin Investig Drugs. 2001;10:1243-53. doi: 10.1517/13543784.10.7.1243. PMID: 11772248.
Sanyal AJ, Ratziu V, Loomba R, Anstee QM, Kowdley KV, Rinella ME, et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. J Hepatol. 2023;79:1110-20. doi: 10.1016/j.jhep.2023.07.014. PMID: 37517454.
Rinella ME, Dufour JF, Anstee QM, Goodman Z, Younossi Z, Harrison SA, 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. PMID: 34793868.
Wang W, Zhao J, Gui W, Sun D, Dai H, Xiao L, et al. Tauroursodeoxycholic acid inhibits intestinal inflammation and barrier disruption in mice with non-alcoholic fatty liver disease. Br J Pharmacol. 2018;175:469-84. doi: 10.1111/bph.14095. PMID: 29139555.
Lu Q, Jiang Z, Wang Q, Hu H, Zhao G. The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation. Ann Hepatol. 2021;23:100289. doi: 10.1016/j.aohep.2020.100289. PMID: 33217585.
Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, et al. Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology. 2020;72:58-71. doi: 10.1002/hep.31205. PMID: 32115759.
Alkhouri N, Herring R, Kabler H, Kayali Z, Hassanein T, Kohli A, et al. Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. J Hepatol. 2022;77:607-18. doi: 10.1016/j.jhep.2022.04.003. PMID: 35439567.
Traussnigg S, Schattenberg JM, Demir M, Wiegand J, Geier A, Teuber G, et al. Norursodeoxycholic acid versus placebo in the treatment of non-alcoholic fatty liver disease: a double-blind, randomised, placebo-controlled, phase 2 dose-finding trial. Lancet Gastroenterol Hepatol. 2019;4:781-93. doi: 10.1016/S2468-1253(19)30184-0. PMID: 31345778.
Carlsson B, Lindén D, Brolén G, Liljeblad M, Bjursell M, Romeo S, et al. Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2020;51:1305-20. doi: 10.1111/apt.15738. PMID: 32383295.
Sanyal AJ, Newsome PN, Kliers I, Østergaard LH, Long MT, Kjær MS, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089-99. doi: 10.1056/NEJMoa2413258. PMID: 40305708.
Alkhouri N. Recent Data from the ESSENCE Trial on Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. Gastroenterol Hepatol (N Y). 2025;21(2):133-5. PMID: 40115605.
Luo S, Liu H, Jin W. Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;393(8):826. doi: 10.1056/NEJMc2509454. PMID: 40834308.
Kim Y, Zeng N, Winer-Jones JP, Bonafede M, Lobo F, O’Donnell J, et al. Retrospective Study of Real-World Treatment Patterns of Subcutaneous Semaglutide Use Among Patients with Metabolic Dysfunction-Associated Steatohepatitis in the United States. Clinicoecon Outcomes Res. 2025; 17:743-54. doi: 10.2147/CEOR.S546841. PMID: 41147033.
Fiorucci S, Urbani G. Tirzepatide for metabolic dysfunction-associated steatohepatitis: results from phase II clinical trials and perspectives. Expert Opin Investig Drugs. 2025;34(9):655-63. doi: 10.1080/13543784.2025.2546812. PMID: 40782123.
Arai T, Atsukawa M, Nagao C, Yamada Z, Rokugo T, Suzuki K, et al. Effect of Tirzepatide Treatment on Hepatic Biomarkers in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Mellitus. Hepatol Res. 2025;55(10):1346-52. doi: 10.1111/hepr.14241. PMID: 40616360.
Li Y, Sun W, Liu H, Ruan XZ. Tirzepatide, a dual GIP/GLP-1 receptor agonist, alleviates metabolic dysfunctionassociated steatotic liver disease by reducing the expression of CD36 and OBP2A. Genes Dis. 2025;12(6):101761. doi: 10.1016/j.gendis.2025.101761. PMID: 40837406.
Reja D, Zhang C, Sarkar A. Endoscopic bariatrics: current therapies and future directions. Transl Gastroenterol Hepatol. 2022;7:21. doi: 10.21037/tgh.2020.03.09. PMID: 35548475.
Moutzoukis MK, Argyriou K, Manolakis A, Kapsoritakis A, Christodoulou D. Endoscopic bariatrics: Current status and emerging technologies. World J Gastrointest Endosc 2025;17(10):109031. doi: 10.4253/wjge.v17.i10.109031. PMID: 41181529.
Mingrone G, Rajagopalan H. Bariatrics and endoscopic therapies for the treatment of metabolic disease: Past, present, and future. Diabetes Res Clin Pract. 2024;211:111651. doi: 10.1016/j.diabres.2024.111651.
PMID: 38580037.
Younossi ZM, Stepanova M, Ong J, Trimble G, AlQahtani S, Younossi I, et al. Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States. Clin Gastroenterol Hepatol. 2021; 19(3):580-9.e5. doi: 10.1016/j.cgh.2020.05.064. PMID: 32531342.
Lim TY, Steggerda JA, Trivedi H, Luu M, Vipani A, Adjei MA, et al. Outcomes from Referral to Transplant for Patients with MASLD: A California Liver Network Study. J Clin Med. 2025;14(21):7841. doi: 10.3390/jcm14217841. PMID: 41227237.
Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, et al. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology. 2018;154(6):1706-18.e1. doi: 10.1053/j.gastro.2018.01.064. PMID: 29425931.
Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681-93. doi: 10.1016/j.jhep.2021.11.018. PMID: 34801630.
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Copyright (c) 2026 Enver Zerem, Azra Husić, Maja Karin, Tanja Glamočanin, Mirela Bašić Denjagić, Emil Babić, Zumreta Bihorac- Kučuk, Goran Bokan, Nerma Čustović, Aida Dumpor, Belma Hadžiselimović, Admir Kurtcehajic, Ljubica Jovandić, Predrag Jovanović, Amila Mehmedović, Nataša Pilipović-Broćeta, Dženita Salihefendić, Nadža Zubčević

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