REFERENCES
1. Byrne CD, Armandi A, Pellegrinelli V, Vidal-Puig A, Bugianesi E. Μetabolic dysfunction-associated steatotic liver disease: a condition of heterogeneous metabolic risk factors, mechanisms and comorbidities requiring holistic treatment. Nat Rev Gastroenterol Hepatol. 2025;22:314-28.
2. Zhu Y, Cai B. Mechanisms and therapeutic insights into MASH-associated fibrosis. Trends Endocrinol Metab. 2026;37:402-17.
3. Yeo YH, Abdelmalek M, Khan S, et al. Current and emerging strategies for the prevention of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2025;22:173-90.
4. Ma X, Song J, Hong X, Lin Z. Genetically informed single-cell analysis reveals PLXND1 as a cell-type-specific molecular switch in MASLD. Metabolites. 2026;16:378.
5. Hanna S, Sethiadi J, Ali Q, Sinha S. Repurposing GLP-1 Receptor Agonists: a perspective on epigenetic strategies to combat fibrosis and hepatocellular carcinoma in the aged liver. Cancers. 2025;17:2600.
6. Anton A, Friedman SL, Cogliati B. Hepatic fibrosis and liver cancer. Semin Liver Dis. 2026;46:31-50.
7. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5:245-66.
8. Allen AM, Arab JP, Wong VW. MASLD: a disease in flux. Nat Rev Gastroenterol Hepatol. 2024;21:747-50.
9. Rinella ME, Lazarus JV, Ratziu V, et al. ; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79:1542-56.
10. Loomba R, Wong VW. Implications of the new nomenclature of steatotic liver disease and definition of metabolic dysfunction-associated steatotic liver disease. Aliment Pharmacol Ther. 2024;59:150-6.
11. Park H, Cheuk-Fung Yip T, Yoon EL, et al. Impact of cardiometabolic risk factors on hepatic fibrosis and clinical outcomes in MASLD: a population-based multi-cohort study. JHEP Rep. 2025;7:101388.
12. Friedman SL, Pinzani M. Hepatic fibrosis 2022: unmet needs and a blueprint for the future. Hepatology. 2022;75:473-88.
13. Hemmann S, Graf J, Roderfeld M, Roeb E. Expression of MMPs and TIMPs in liver fibrosis - a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol. 2007;46:955-75.
14. Roeb E. Matrix metalloproteinases and liver fibrosis (translational aspects). Matrix Biol. 2018;68-69:463-73.
15. Hempel F, Roderfeld M, Savai R, et al. Depletion of bone marrow-derived fibrocytes attenuates TAA-induced liver fibrosis in mice. Cells. 2019;8:1210.
16. Schwabe RF, Tacke F, Sugimoto A, Friedman SL. Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease. JHEP Rep. 2025;7:101421.
17. Kuwano A, Miyazaki M, Yada M, et al. FIB‑4 index and serum α‑fetoprotein are useful predictors of hepatocellular carcinoma occurrence in hepatitis B patients with nucleos(t)ide analogs therapy. Exp Ther Med. 2023;26:441.
18. Xue Y, Tian T, Ottallah M, et al. Alcohol-associated hepatocarcinogenesis: Wnt/β-catenin in action. Am J Pathol. 2026;196:151-60.
19. Pennisi G, Infantino G, Di Maria G, et al. One-year changes in liver stiffness measurement, but not in alanine aminotransferase and controlled attenuation parameter, predict long-term liver outcomes in patients with metabolic dysfunction-associated steatotic liver disease. Clin Gastroenterol Hepatol. 2026;24:2474-85.
20. 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;81:492-542.
21. Roeb E, Canbay A, Bantel H, et al. ; Collaborators. Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) - April 2022 - AWMF-Registernummer: 021-025. Z Gastroenterol. 2022;60:1346-421.
22. Miller DM, McCauley KF, Dunham-Snary KJ. Metabolic dysfunction-associated steatotic liver disease (MASLD): mechanisms, clinical implications and therapeutic advances. Endocrinol Diabetes Metab. 2025;8:e70132.
23. Zhao Q, Lu S, Guan Y, Sun Z, Qiu S, Zhang A. Dysregulation of the AMPK-SREBP1-FASN axis in MASLD: driving a vicious cycle of lipotoxicity and metabolic-immune crosstalk. Lipids Health Dis. 2026;25:62.
24. Tilg H, Petta S, Stefan N, Targher G. Metabolic dysfunction-associated steatotic liver disease in adults: a review. JAMA. 2026;335:163-74.
25. Farrell GC, Haczeyni F, Chitturi S. Pathogenesis of NASH: how metabolic complications of overnutrition favour lipotoxicity and pro-inflammatory fatty liver disease. Adv Exp Med Biol. 2018;1061:19-44.
26. Fomin M, Zapf K, Schieffer E, Freitag J, Bange G, Schieffer B. From lipid overload to autophagy collapse: how lipid dysregulation drives chronic inflammation and metabolic disease. Inflamm Res. 2026;75:138.
27. de la Lastra JMP, Andrés CMC, Munguira EB, Juan CA, Pérez-Lebeña E. Pathophysiology of reactive oxygen species (ROS). Arch Toxicol. 2026;100:475-513.
28. Mohammed S, Jiang C, Pennington T, et al. A non-canonical role for hepatocyte MLKL in promoting mitochondrial dysfunction and senescence in the aging liver. Aging Cell. 2026;25:e70618.
29. Behari J, Gougol A, Wang R, et al. Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis. Hepatol Commun. 2023;7:e00183.
30. Romeo M, Silvestrin A, Senese G, et al. From “traditional” to “trained” immunity: exploring the novel frontiers of immunopathogenesis in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Biomedicines. 2025;13:2004.
31. Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol. 2018;68:526-49.
32. Li X, Lebeaupin C, Kadianaki A, et al. Activated ATF6α is a hepatic tumour driver restricting immunosurveillance. Nature. 2026;651:796-807.
33. Ismaiel A, Almonajjed MB, Wardeh M, et al. From dysbiosis to malignancy: decoding gut-driven pathways to clinical management in hepatocellular carcinoma. Front Cell Infect Microbiol. 2026;16:1852380.
34. Duan L, Chang Y, Dai J, et al. Lipid metabolism orchestrates liver regeneration: an integrated metabolic network. J Transl Med. 2025;23:1115.
35. Do A, Zahrawi F, Mehal WZ. Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH). Nat Rev Drug Discov. 2025;24:171-89.
36. Friedline RH, Noh HL, Suk S, et al. IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease. Nat Commun. 2024;15:5506.
37. Bansal SK, Bansal MB. Pathogenesis of MASLD and MASH - role of insulin resistance and lipotoxicity. Aliment Pharmacol Ther. 2024;59:S10-22.
38. Díaz LA, Arab JP, Louvet A, Bataller R, Arrese M. The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2023;20:764-83.
39. Díaz LA, Pose E, Israelsen M, Loomba R. Global epidemiology of metabolic and alcohol-associated liver disease: risk factors, natural history and clinical implications. Nat Rev Gastroenterol Hepatol. 2026;Epub ahead of print.
40. Diaz LA, Arab JP, Idalsoaga F, et al. Updated recommendations for the management of metabolic dysfunction-associated steatotic liver disease (MASLD) by the Latin American working group. Ann Hepatol. 2025;30:101903.
41. Hammerich L, Tacke F. Hepatic inflammatory responses in liver fibrosis. Nat Rev Gastroenterol Hepatol. 2023;20:633-46.
42. González-Serrano S, Onoiu AI, Camps J, Joven J. Immunometabolic integration in therapeutic strategies for managing MASLD. Front Pharmacol. 2025;16:1693753.
43. Diaz LA, Thiele M, Louvet A, et al. Clinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease. Nat Rev Gastroenterol Hepatol. 2025;22:866-84.
44. Schwärzler J, Grabherr F, Grander C, Adolph TE, Tilg H. The pathophysiology of MASLD: an immunometabolic perspective. Expert Rev Clin Immunol. 2024;20:375-86.
45. Shera S, Katzka W, Yang JC, et al. Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system. Front Microbiol. 2024;15:1407555.
46. Wang H, Tsung A, Zhang H. Neutrophil extracellular traps: a central player in liver diseases. Hepatol Commun. 2026;10:e0970.
47. Supruniuk E, Grubczak K, Parfieniuk-Kowerda A, et al. Increased frequencies of human Th-17 CD4+ T-cells and decreased T-regulatory cells in patients with early and advanced metabolic dysfunction-associated steatotic liver disease. Front Immunol. 2025;16:1597204.
48. Schmid A, Arians M, Burg-Roderfeld M, et al. Circulating adipokines and hepatokines serve as diagnostic markers during obesity therapy. Int J Mol Sci. 2022;23:14020.
49. Ramirez CFA, Taranto D, Ando-Kuri M, et al. Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma. Nat Commun. 2024;15:2581.
50. Schwabe RF, Tabas I, Pajvani UB. Mechanisms of fibrosis development in nonalcoholic steatohepatitis. Gastroenterology. 2020;158:1913-28.
51. Colella F, Henderson NC, Ramachandran P. Dissecting the mechanisms of MASLD fibrosis in the era of single-cell and spatial omics. J Clin Invest. 2025;135:e186421.
52. Chen X, Zhou Z, Xie L, et al. Single-cell resolution spatial analysis of antigen-presenting cancer-associated fibroblast niches. Cancer Cell. 2025;43:2224-40.e9.
53. Suo Y, Thimme R, Bengsch B. Spatial single-cell omics: new insights into liver diseases. Gut. 2026;75:1248-63.
54. Liu Q, Wang C, Ye C, et al. Integrated multi-omics, spatial profiling and organoid modeling drive transformative advances in chronic liver disease and hepatocellular carcinoma immunomicroenvironment research. Front Immunol. 2026;17:1743439.
55. Matsuda M, Seki E. The liver fibrosis niche: novel insights into the interplay between fibrosis-composing mesenchymal cells, immune cells, endothelial cells, and extracellular matrix. Food Chem Toxicol. 2020;143:111556.
56. Novoa E, Parracho T, Inderhees J, et al. Lack of PCK1 in hepatic stellate cells causes liver fibrosis by fueling tricarboxylic acid cycle and increasing glycolysis. Cell Metab. 2026;38:729-45.e9.
57. Zhang X, Sharma P, Maschmeyer P, et al. GARP on hepatic stellate cells is essential for the development of liver fibrosis. J Hepatol. 2023;79:1214-25.
58. Chaudhary R, Weiskirchen R, Ehrlich M, Henis YI. Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression. Front Pharmacol. 2025;16:1580500.
59. Mostafa S, Shetab Boushehri MA, Ezzat AA, et al. Targeted delivery of anti-TGF-β(1)-siRNA using PDGFR-β peptide-modified chitosan nanoparticles for the treatment of liver fibrosis. Mol Pharm. 2025;22:6741-58.
60. Benhammou JN, Qiao B, Ko A, Sinnett-Smith J, Pisegna JR, Rozengurt E. Lipophilic statins inhibit YAP coactivator transcriptional activity in HCC cells through Rho-mediated modulation of actin cytoskeleton. Am J Physiol Gastrointest Liver Physiol. 2023;325:G239-50.
61. Ma J, Xie N, Wang Z, et al. Liver stiffness rises early in MASLD and drives inflammation, lipid dysmetabolism, and fibrosis via Piezo1-YAP mechanotransduction. Adv Sci. 2026;13:e19109.
62. Muto H, Kubara K, Hitaoka S, Osada Y, Suzuki Y. Ionizable lipid chemistry in lipid nanoparticles determines delivery efficiency to hepatic stellate cells. J Control Release. 2025;385:114055.
63. Roderfeld M, Weiskirchen R, Wagner S, et al. Inhibition of hepatic fibrogenesis by matrix metalloproteinase-9 mutants in mice. FASEB J. 2006;20:444-54.
64. Bitar M, Samyn D, Helgesson M, Pettersson-Pablo P, Vink M. Preanalytical effects on the ELF score and its component biomarkers; aminoterminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA) and tissue inhibitor of metalloproteinases-1 (TIMP-1). Scand J Clin Lab Invest. 2026;86:374-83.
65. Vali Y, van Dijk AM, Lee J, et al. ; LITMUS investigators. Precision in liver diagnosis: varied accuracy across subgroups and the need for variable thresholds in diagnosis of MASLD. Liver Int. 2025;45:e16240.
66. Schuppan D, Myneni S, Surabattula R. Liquid biomarkers for fibrotic NASH - progress in a complex field. J Hepatol. 2022;76:5-7.
67. Baptista C, Esteves F, Fallowfield JA, Kendall TJ, Nelson LJ, Kranendonk M. Deciphering cytochrome P450 reductase role in MASLD: molecular mechanisms and pathophysiological implications. Nat Rev Gastroenterol Hepatol. 2026;23:655-68.
68. Jurnečka D, Hrovatin M, Bokalj B, Turk B. Proteolysis at the extracellular matrix interface: Molecular architects and regulators in health and disease. FEBS J. 2026;293:3758-87.
69. Hachiya R, Tanaka M, Itoh M, Suganami T. Molecular mechanism of crosstalk between immune and metabolic systems in metabolic syndrome. Inflamm Regen. 2022;42:13.
70. Gastaldelli A, Scoditti E, Macedo MP. Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis. Diabetologia. 2026;69:3088-104.
71. Kwapisz O, Marona P, Gorka J, et al. The endonuclease MCPIP1 protects against liver cancer development in a sex-dependent manner by modulating β-catenin and CREB1. JHEP Rep. 2026;8:101755.
72. Mitten EK, Baffy G. Mechanotransduction in the pathogenesis of non-alcoholic fatty liver disease. J Hepatol. 2022;77:1642-56.
73. Fan Z, Deng K, Wang L, et al. The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression. Front Immunol. 2026;17:1849447.
74. Kockar F, Tokay E, Hacioglu N, et al. Oxygen-dependent regulation of ADAMTS1 by VEGFA defines a novel VEGFA-HIF-ADAMTS1 axis in hepatocellular cancer. Tissue Cell. 2026;100:103395.
75. Gahr S, Mayr C, Kiesslich T, et al. The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression. Int J Oncol. 2015;47:963-70.
76. Yang YM, Kim J, Wang Z, et al. Metastatic tumor growth in steatotic liver is promoted by HAS2-mediated fibrotic tumor microenvironment. J Clin Invest. 2025;135:e180802.
77. Bingham NE, Boiko JR, Jones DC, et al. Spatial transcriptomics identifies a suppressive, T-cell-excluded tumor microenvironment in extramedullary myeloma. Blood Adv. 2026;10:6221-35.
78. Beudeker BJB, Groothuismink ZMA, van der Eijk AA, Debes JD, Boonstra A. Circulating cytokines reflect the etiology-specific immune environment in cirrhosis and HCC. Cancers. 2022;14:4900.
79. Shah DD, Dave BP, Patel PA, et al. Revamping the innate or innate-like immune cell-based therapy for hepatocellular carcinoma: new mechanistic insights and advanced opportunities. Med Oncol. 2023;40:84.
80. Wu Q, Sun Q, Zhang Q, Wang N, Lv W, Han D. Extracellular matrix stiffness-induced mechanotransduction of capillarized liver sinusoidal endothelial cells. Pharmaceuticals. 2024;17:644.
81. Kleffel S, Schatton T. Tumor dormancy and cancer stem cells: two sides of the same coin? Adv Exp Med Biol 2013;734:145-79.
82. Schmittnaegel M, De Palma M. Reprogramming tumor blood vessels for enhancing immunotherapy. Trends Cancer. 2017;3:809-12.
83. Wang L, Shao Z, Wang X, Lu W, Sun H. Xenobiotic-induced liver injury: molecular mechanisms and disease progression. Ecotoxicol Environ Saf. 2025;303:118854.
84. Massoudi D, Srivastava A, Dhanasekaran R. Unraveling the tapestry: lessons from multi-omics and spatial biology in hepatocellular cancer. Hepatology. 2026;84:1229-45.
85. Celik F, Yuksel M, Bektas H. Effect of E-Health-Assisted lifestyle interventions on weight loss in patients with metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD): a meta-analysis. West J Nurs Res. 2026;48:323-38.
86. Roeb E, Canbay A, Bantel H, et al. ; für die Autoren des DGVS Leitlinienkomitees/for the authors of the DGVS guideline committee, Collaborators. [Amendment “Resmetirom” to the S2k guideline “Metabolic Liver Diseases” (formerly “Non-Alcoholic Fatty Liver Disease” v.2.0/April 2022) of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) (Version 2.3)]. Z Gastroenterol. 2026;64:386-413.
87. Keating SE, Sabag A, Hallsworth K, et al. Exercise in the management of metabolic-associated fatty liver disease (MAFLD) in adults: a position statement from exercise and sport science Australia. Sports Med. 2023;53:2347-71.
88. Wang Y, Wan S. Mitochondrial MFN2 integrates the function of multiple organelles to regulate metabolic dysfunction-associated steatotic liver disease: mechanisms and therapeutic insights. Biochem Pharmacol. 2025;242:117423.
89. Hawley JA, Hargreaves M, Joyner MJ, Zierath JR. Integrative biology of exercise. Cell. 2014;159:738-49.
90. Roeb E. Diagnostic and therapy of nonalcoholic fatty liver disease: a narrative review. Visc Med. 2022;38:126-32.
91. 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. Lancet. 2023;401:1786-97.
92. Lin RT, Sun QM, Xin X, et al. Comparative efficacy of THR-β agonists, FGF-21 analogues, GLP-1R agonists, GLP-1-based polyagonists, and Pan-PPAR agonists for MASLD: A systematic review and network meta-analysis. Metabolism. 2024;161:156043.
93. Allen AM, Younossi ZM, Diehl AM, Charlton MR, Lazarus JV. Envisioning how to advance the MASH field. Nat Rev Gastroenterol Hepatol. 2024;21:726-38.
94. Romero-Gómez M, Lawitz E, Shankar RR, et al. ; MK-6024 P001 Study Group. A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. J Hepatol. 2023;79:888-97.
95. Sanyal AJ, Newsome PN, Kliers I, et al. ; ESSENCE Study Group. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392:2089-99.
96. Newsome PN, Ambery P. Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver. J Hepatol. 2023;79:1557-65.
97. 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;73:757-70.
98. Newsome PN, Loomba R. Therapeutic horizons in metabolic dysfunction-associated steatohepatitis. J Clin Invest. 2025;135:e186425.
99. Liu W, You D, Lin J, et al. SGLT2 inhibitor promotes ketogenesis to improve MASH by suppressing CD8+ T cell activation. Cell Metab. 2024;36:2245-61.e6.
100. da Silva Lima N, Cabaleiro A, Novoa E, et al. GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells. Cell Mol Life Sci. 2024;81:468.
101. Yabut JM, Drucker DJ. Glucagon-like peptide-1 receptor-based therapeutics for metabolic liver disease. Endocr Rev. 2023;44:14-32.
102. Ye B, Xu C. Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2026;32:1158-85.
103. Marawan AE, Elmetwally OA, Abass SA, Marwan MM, El-Sokkary MMA, Eissa LA. Microbiome/transforming growth factor-β axis as a diagnostic and therapeutic target for MASLD in Egyptian patients. Gut Pathog. 2026;18:33.
104. Cao L, Zhao Y. Apigenin attenuates hepatocyte senescence in metabolic dysfunction-associated steatotic liver disease by targeting the TGF-β signaling pathway. Cytotechnology. 2026;78:149.
105. Huang LJ, Wang MY, Xin FZ, et al. Sodium butyrate ameliorates liver fibrosis in metabolic dysfunction-associated steatohepatitis rats via miR-155-5p/SOCS1/PDGF signaling pathway. Hepatobiliary Pancreat Dis Int. 2025;24:423-32.
106. Pollheimer MJ, Racedo S, Mikels-Vigdal A, et al. Lysyl oxidase-like protein 2 (LOXL2) modulates barrier function in cholangiocytes in cholestasis. J Hepatol. 2018;69:368-77.
107. Scavo MP, Lisco G, Depalo N, et al. Semaglutide modulates extracellular matrix production of LX-2 cells via exosomes and improves metabolic dysfunction-associated steatotic liver disease (MASLD). Int J Mol Sci. 2024;25:1493.
108. Sedda F, Caddeo A, Sasidharan K, et al. Galectin-3 inhibition ameliorates hepatic steatosis in a multilineage 3D spheroid model. PLoS One. 2025;20:e0326373.
109. Mehtab A, Ali H, Ali I, et al. Exploring the inhibitory effects of compounds for the treatment of liver fibrosis: a computational and microscopic approach. Curr Pharm Des. 2026;32:2311-35.
110. Jun JH, Dutta RK, Cho SW, et al. Hepatocyte hedgehog signaling controls ferroptosis to alleviate aging-related organ dysfunction. JCI Insight. 2026;11:e207066.
111. Muturi HT, Ghadieh HE, Asalla S, et al. Conditional deletion of CEACAM1 in hepatic stellate cells causes their activation. Mol Metab. 2024;88:102010.
112. Tacke F, Weiskirchen R. Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH)-related liver fibrosis: mechanisms, treatment and prevention. Ann Transl Med. 2021;9:729.
113. Chen G, Yu Y, Zhu Y, et al. Cenicriviroc suppresses and reverses steatohepatitis by regulating macrophage infiltration and M2 polarization in mice. Endocrinology. 2024;165:bqae069.
114. Feng P, Su H, Wang W, et al. Ferulic acid ameliorates metabolic dysfunction associated with fatty liver disease by regulating macrophage polarization through spermidine derived from gut microbiota. J Pharm Pharmacol. 2026;78:rgag055.
115. Tsakiridis EE, Steinberg GR. Incretin and glucagon signalling in MASLD and MASH: integrating metabolic pathways with disease progression. Diabetes Obes Metab. 2026;28:31-45.
116. Barrett R, Archer A, Cathcart J, Abeysekera K, Dillon JF, Brennan PN. Progression to decompensation of severe fibrosis compared to cirrhosis in MASLD: a systematic review and meta-analysis. Liver Int. 2026;46:e70511.
117. Shang Y, Vessby J, Kant Mangla K, et al. Association between invasive and noninvasive liver disease assessments and long-term clinical outcomes in MASLD. Scand J Gastroenterol. 2025;60:1226-37.
118. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367-78.e5.
119. Vilar-Gomez E, Nephew LD, Vuppalanchi R, et al. High-quality diet, physical activity, and college education are associated with low risk of NAFLD among the US population. Hepatology. 2022;75:1491-506.
120. Thiele M, Kamath PS, Graupera I, et al. Screening for liver fibrosis: lessons from colorectal and lung cancer screening. Nat Rev Gastroenterol Hepatol. 2024;21:517-27.
121. Lindvig KP, Thorhauge KH, Hansen JK, et al. Development, validation, and prognostic evaluation of LiverPRO for the prediction of significant liver fibrosis in primary care: a prospective cohort study. Lancet Gastroenterol Hepatol. 2025;10:55-67.
122. Wei L, Gao C, Qin H. Comparison and characteristics of MASLD mouse models. Biomedicines. 2026;14:895.
123. Gallage S, Castro RE, Estall J, et al. EASL position paper on preclinical models of steatotic liver disease. J Hepatol. 2026;85:345-82.
124. Alavala S, Sharma N, Sangaraju R, Challa S, Sistla R, Andugulapati SB. Stevioside alleviates high-fat diet-induced MASLD in Apo-E‑/‑ mice by modulating the TGF-β signaling. J Nutr Biochem. 2026;147:110125.
125. Srinivas AN, Suresh D, Chidambaram SB, Santhekadur PK, Kumar DP. Apoptosis antagonizing transcription factor-mediated liver damage and inflammation to cancer: therapeutic intervention by curcumin in experimental metabolic dysfunction associated steatohepatitis-hepatocellular carcinoma. J Cell Physiol. 2024;239:135-51.
126. Kuang X, Naiki-Ito A, Kawamura H, et al. Hepatic stellate cell inhibition by angiotensin II receptor blocker mitigates liver injury and fibrosis via NF-κB-galectin-3 suppression in a rat nonalcoholic steatohepatitis model. Arch Toxicol. 2025;99:3393-412.
127. Wang H, Wang G, Yin T, et al. AMPK maintains the activation of hepatic stellate cells through mitophagy-induced metabolic reprogramming. J Mol Cell Biol. 2026;17:mjaf030.
128. Akuta N, Kogiso T, Ikejima K, et al. Evidence-based clinical practice guidelines for metabolic dysfunction-associated steatotic liver disease (MASLD) 2026. J Gastroenterol. 2026;61:693-710.
129. Dua A, Kumari R, Singh M, et al. Metabolic dysfunction-associated steatotic liver disease (MASLD): the interplay of gut microbiome, insulin resistance, and diabetes. Front Med. 2025;12:1618275.
130. Simon TG, Roelstraete B, Sharma R, Khalili H, Hagström H, Ludvigsson JF. Cancer risk in patients with biopsy-confirmed nonalcoholic fatty liver disease: a population-based cohort study. Hepatology. 2021;74:2410-23.
131. Morgan TR, Ghany MG, Kim HY, et al. ; HALT-C Trial Group. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010;52:833-44.
132. Lockart I, Yeo MGH, Hajarizadeh B, Dore GJ, Danta M. HCC incidence after hepatitis C cure among patients with advanced fibrosis or cirrhosis: a meta-analysis. Hepatology. 2022;76:139-54.
133. Affo S, Yu LX, Schwabe RF. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu Rev Pathol. 2017;12:153-86.
134. Borz-Baba L, Aydin A, Parvin R. Liver biopsy in metabolic-associated steatotic liver disease: accuracy, challenges, and alternatives. Cureus. 2026;18:e103284.
135. Younossi ZM, de Avila L, Petta S, et al. ; Global NASH/MASH Council (GNC). Predictors of fibrosis, clinical events, and mortality in MASLD: data from the Global-MASLD study. Hepatology. 2026;84:204-15.
136. Harrison SA, Ratziu V, Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. 2020;5:970-85.
137. Matchett KP, Paris J, Teichmann SA, Henderson NC. Spatial genomics: mapping human steatotic liver disease. Nat Rev Gastroenterol Hepatol. 2024;21:646-60.
139. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14:397-411.
140. Trautwein C, Friedman SL, Schuppan D, Pinzani M. Hepatic fibrosis: concept to treatment. J Hepatol. 2015;62:S15-24.
141. Yang LX, Qi C, Lu S, et al. Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells. Nat Commun. 2025;16:524.
142. Koda Y, Teratani T, Chu PS, et al. CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells. Nat Commun. 2021;12:4474.
143. Harrison SA, Bedossa P, Guy CD, et al. ; MAESTRO-NASH Investigators. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390:497-509.
144. Francque SM, Bedossa P, Ratziu V, et al. ; NATIVE Study Group. A randomized, controlled trial of the Pan-PPAR agonist lanifibranor in NASH. N Engl J Med. 2021;385:1547-58.
145. Loomba R, Hartman ML, Lawitz EJ, et al. ; SYNERGY-NASH Investigators. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med. 2024;391:299-310.
146. Noureddin M, Frias JP, Neff GW, et al. Safety and efficacy of once-weekly efruxifermin versus placebo in metabolic dysfunction-associated steatohepatitis (HARMONY): 96-week results from a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2025;406:719-30.
147. Harrison SA, Frias JP, Neff G, et al. ; HARMONY Study Group. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2023;8:1080-93.
148. Loomba R, Sanyal AJ, Kowdley KV, et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH. N Engl J Med. 2023;389:998-1008.
149. Younossi ZM, Ratziu V, Loomba R, et al. ; REGENERATE Study Investigators. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019;394:2184-96.
150. Anstee QM, Neuschwander-Tetri BA, Wai-Sun Wong V, et al. Cenicriviroc lacked efficacy to treat liver fibrosis in nonalcoholic steatohepatitis: AURORA phase III randomized study. Clin Gastroenterol Hepatol. 2024;22:124-34.e1.
151. Harrison SA, Wong VW, Okanoue T, et al. ; STELLAR-3, STELLAR-4 Investigators. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials. J Hepatol. 2020;73:26-39.
152. Priego-Parra BA, Gallego-Durán R, Román-Calleja BM, Velarde-Ruiz Velasco JA, Romero-Gómez M, Gracia-Sancho J. Advancing precision medicine in metabolic dysfunction-associated steatotic liver disease. Trends Endocrinol Metab. 2025;36:1000-13.
153. Chen VL, Kuppa A, Oliveri A, et al. Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment. J Clin Invest. 2025;135:e186424.
154. Chen Y, Laevens BPM, Lemainque T, et al. Deep learning reveals liver MRI features associated with PNPLA3 I148M in steatotic liver disease. Liver Int. 2025;45:e70164.
155. Targher G, Byrne CD, Tilg H. MASLD: a systemic metabolic disorder with cardiovascular and malignant complications. Gut. 2024;73:691-702.
156. Mantovani A, Lonardo A, Stefan N, Targher G. Metabolic dysfunction-associated steatotic liver disease and extrahepatic gastrointestinal cancers. Metabolism. 2024;160:156014.




