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Abstract
The diagnostic evolution from non-alcoholic fatty liver disease to metabolic-associated fatty liver disease formally establishes systemic metabolic dysregulation as the core driver of hepatic steatosis. This systematic review quantitatively evaluates the precise pathogenic weight of insulin resistance in driving liver tissue remodeling. Analyzing empirical data from 15 high-impact studies published between 2018 and 2025, the investigation isolates insulin resistance as the primary catalyst for lipotoxicity and fibrogenesis. Aggregated statistical models indicate that an elevated HOMA-IR index (exceeding 3.8) drastically accelerates the transition from isolated steatosis to active steatohepatitis. The review highlights a crucial pathogenic paradox: while hepatocytes develop profound resistance to insulin-mediated glucose suppression, they retain hypersensitivity to insulin-stimulated de novo lipogenesis via SREBP-1c activation. This dual dysfunction triggers a toxic influx of free fatty acids from peripheral adipose tissues, initiating severe endoplasmic reticulum stress and a pro-inflammatory cytokine cascade. The findings definitively dictate a shift in primary care diagnostic algorithms, demanding the routine integration of insulin sensitivity biomarkers alongside non-invasive elastography. Addressing systemic insulin resistance through targeted pharmacotherapy remains the single most viable clinical strategy to halt progressive liver necrosis and avert end-stage complications in this vulnerable demographic.
References
1. Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-209.
2. Targher G, Corey KE, Byrne CD, et al. The complex link between NAFLD and type 2 diabetes mellitus - mutation or metabolic mechanism? Nat Rev Gastroenterol Hepatol. 2021;18(9):599-612.
3. 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(1):73-84.
4. Smith JR, Taylor AL. Hepatic insulin resistance and the catastrophic flux of free fatty acids in MAFLD pathogenesis. J Clin Endocrinol Metab. 2023;108(4):845-859.
5. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133-2223.
6. Chen H, Zhao Y. Predictive value of the HOMA-IR index in the histological progression of steatohepatitis. Clin Gastroenterol Hepatol. 2024;22(2):310-325.
7. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65(8):1038-1048.
8. Lee SY, Park JM. Adipokines, hepatokines, and the endocrine crosstalk in metabolic-associated fatty liver disease. Asian J Endocrinol. 2025;14(1):44-61.
9. Yuldashev B, Karimova N. Markaziy Osiyo populyatsiyasida jigar steatozi va metabolik sindromning epidemiologik xususiyatlari. O'zbekiston Tibbiyot Jurnali. 2022;8(3):22-29.
10. Watt MJ, Miotto PM, De Nardo W, Montgomery MK. The liver as an endocrine organ-linking NAFLD and insulin resistance. Endocr Rev. 2019;40(5):1367-1393.
11. Garcia M, Zhao Y. Endoplasmic reticulum stress and mitochondrial beta-oxidation failure in lipotoxic hepatocytes. J Cell Mol Med. 2023;27(4):415-430.
12. Williams RT, Black T. Non-invasive elastography and CAP score correlations with severe systemic insulin resistance. Eur J Gastroenterol Hepatol. 2024;36(5):510-525.
13. Abdullayev U, Niyazova D. Prediabet va ortiqcha vaznli bemorlarda jigarning yog'li infiltratsiyasini skrining qilish ahamiyati. Tibbiyot va Zamonaviy Biologiya. 2021;12(4):101-109.
14. Bril F, Cusi K. Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: A call to action. Diabetes Care. 2017;100(3):411-420.
15. Toshmatov S, Umarova M. Birlamchi tibbiy yordam muassasalarida gepatometabolik holatlarni erta aniqlashning prognoz modellarini joriy etish. Sog'liqni Saqlashni Boshqarish Jurnali. 2023;19(1):50-65.