Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022;7(9):851–61. https://doi.org/10.1016/S2468-1253(22)00165-0.
Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79(6):1542–56. https://doi.org/10.1016/j.jhep.2023.06.003.
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. https://doi.org/10.1016/j.jhep.2020.03.039.
Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966–86. https://doi.org/10.1097/HEP.0000000000000520.
Simon TG, Roelstraete B, Khalili H, Hagstrom H, Ludvigsson JF. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut. 2021;70(7):1375–82. https://doi.org/10.1136/gutjnl-2020-322786.
Sakurai Y, Kubota N, Yamauchi T, Kadowaki T. Role of insulin resistance in MAFLD. Int J Mol Sci. 2021;22(8):4156. https://doi.org/10.3390/ijms22084156.
Ramanathan R, Ali AH, Ibdah JA. Mitochondrial dysfunction plays central role in nonalcoholic fatty liver disease. Int J Mol Sci. 2022;23(13):7280. https://doi.org/10.3390/ijms23137280.
Sun J, Zhang D, Li Y. Extracellular vesicles in pathogenesis and treatment of metabolic associated fatty liver disease. Front Physiol. 2022;13:909518. https://doi.org/10.3389/fphys.2022.909518.
Fred RG, Steen Pedersen J, Thompson JJ, Lee J, Timshel PN, Stender S, et al. Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis. Sci Rep. 2022;12(1):13484. https://doi.org/10.1038/s41598-022-16754-7.
Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol. 2016;13(7):412–25. https://doi.org/10.1038/nrgastro.2016.85.
Lichtman SN, Sartor RB, Keku J, Schwab JH. Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology. 1990;98(2):414–23. https://doi.org/10.1016/0016-5085(90)90833-m.
Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013;57(2):601–9. https://doi.org/10.1002/hep.26093.
Zhang B, Zhao J, Jiang M, Peng D, Dou X, Song Y, et al. The potential role of gut microbial-derived exosomes in metabolic-associated fatty liver disease: implications for treatment. Front Immunol. 2022;13:893617. https://doi.org/10.3389/fimmu.2022.893617.
Boel F, Akimov V, Teuchler M, Terkelsen MK, Wernberg CW, Larsen FT, et al. Deep proteome profiling of metabolic dysfunction-associated steatotic liver disease. Commun Med. 2025;5(1):56. https://doi.org/10.1038/s43856-025-00780-3.
Montgomery MK, Bayliss J, Nie S, De Nardo W, Keenan SN, Miotto PM, et al. Deep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control. Nat Commun. 2022;13(1):1259. https://doi.org/10.1038/s41467-022-28889-2.
Mocciaro G, D’Amore S, Jenkins B, Kay R, Murgia A, Herrera-Marcos LV, et al. Lipidomic approaches to study HDL metabolism in patients with central obesity diagnosed with metabolic syndrome. Int J Mol Sci. 2022;23(12):6786. https://doi.org/10.3390/ijms23126786.
Sehgal R, Kaur N, Maiwall R, Ramakrishna G, Maras JS, Trehanpati N. Plasma proteomic analysis identified proteins associated with faulty neutrophils functionality in decompensated cirrhosis patients with sepsis. Cells. 2022;11(11):1745. https://doi.org/10.3390/cells11111745.
European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): executive summary. Diabetologia. 2024;67(11):2375–92. https://doi.org/10.1007/s00125-024-06196-3.
Lei F, Liu YM, Zhou F, Qin JJ, Zhang P, Zhu L, et al. Longitudinal association between markers of liver injury and mortality in COVID-19 in China. Hepatology. 2020;72(2):389–98. https://doi.org/10.1002/hep.31301.
Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18–35. https://doi.org/10.1038/ajg.2016.517.
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83. https://doi.org/10.1002/hep.28156.
Shen B, Yi X, Sun Y, Bi X, Du J, Zhang C, et al. Proteomic and Metabolomic Characterization of COVID-19 Patient Sera. Cell. 2020;182(1):59–72. https://doi.org/10.1016/j.cell.2020.05.032.
Mallick H, Rahnavard A, McIver LJ, Ma S, Zhang Y, Nguyen LH, et al. Multivariable association discovery in population-scale meta-omics studies. PLoS Comput Biol. 2021;17(11):e1009442. https://doi.org/10.1371/journal.pcbi.1009442.
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607–13. https://doi.org/10.1093/nar/gky1131.
Zhong S, Sun YQ, Huo JX, Xu WY, Yang YN, Yang JB, et al. The gut microbiota-aromatic hydrocarbon receptor (AhR) axis mediates the anticolitic effect of polyphenol-rich extracts from Sanghuangporus. Imeta. 2024;3(2):e180. https://doi.org/10.1002/imt2.180.
Yang F, Zhu B, Ozols E, Bai H, Jiang M, Ma FY, et al. A gradient model of renal ischemia reperfusion injury to investigate renal interstitial fibrosis. Int J Immunopathol Pharmacol. 2024;38:3946320241288426. https://doi.org/10.1177/03946320241288426.
Gwag T, Lee S, Li Z, Newcomb A, Otuagomah J, Weinman SA, et al. Platelet-derived thrombospondin 1 promotes immune cell liver infiltration and exacerbates diet-induced steatohepatitis. JHEP Rep. 2024;6(4):101019. https://doi.org/10.1016/j.jhepr.2024.101019.
Gwag T, Ma E, Zhou C, Wang S. Anti-CD47 antibody treatment attenuates liver inflammation and fibrosis in experimental non-alcoholic steatohepatitis models. Liver Int. 2022;42(4):829–41. https://doi.org/10.1111/liv.15182.
Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA, Network NCR. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53(3):810–20. https://doi.org/10.1002/hep.24127.
Friedman J, Alm EJ. Inferring correlation networks from genomic survey data. PLoS Comput Biol. 2012;8(9):e1002687. https://doi.org/10.1371/journal.pcbi.1002687.
He S, Gu H, Yang J, Su Q, Li X, Qin L. Hemoglobin concentration is associated with the incidence of metabolic syndrome. BMC Endocr Disord. 2021;21(1):53. https://doi.org/10.1186/s12902-021-00719-4.
Giorgio V, Mosca A, Alterio A, Alisi A, Grieco A, Nobili V, et al. Elevated hemoglobin level is associated with advanced fibrosis in pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2017;65(2):150–5. https://doi.org/10.1097/MPG.0000000000001614.
Yang S, Ye Z, Liu M, Zhang Y, Wu Q, Zhou C, et al. Association of serum uric acid with all-cause and cardiovascular mortality among adults with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2023;98(1):49–58. https://doi.org/10.1111/cen.14810.
Kumar R, Porwal YC, Dev N, Kumar P, Chakravarthy S, Kumawat A. Association of high-sensitivity C-reactive protein (hs-CRP) with non-alcoholic fatty liver disease (NAFLD) in Asian Indians: a cross-sectional study. J Family Med Prim Care. 2020;9(1):390–4. https://doi.org/10.4103/jfmpc.jfmpc_887_19.
Chiang CH, Huang CC, Chan WL, Chen JW, Leu HB. The severity of non-alcoholic fatty liver disease correlates with high sensitivity C-reactive protein value and is independently associated with increased cardiovascular risk in healthy population. Clin Biochem. 2010;43(18):1399–404. https://doi.org/10.1016/j.clinbiochem.2010.09.003.
Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397(10290):2212–24. https://doi.org/10.1016/S0140-6736(20)32511-3.
Lian J, Fu J. Pioglitazone for NAFLD patients with prediabetes or type 2 diabetes mellitus: a meta-analysis. Front Endocrinol (Lausanne). 2021;12:615409. https://doi.org/10.3389/fendo.2021.615409.
Karedath J, Javed H, Ahsan Talpur F, Lal B, Kumari A, Kivan H, et al. Effect of Vitamin E on Clinical Outcomes in Patients With Non-alcoholic Fatty Liver Disease: A Meta-Analysis. Cureus. 2022;14(12):e32764. https://doi.org/10.7759/cureus.32764.
Lemoinne S, Friedman SL. New and emerging anti-fibrotic therapeutics entering or already in clinical trials in chronic liver diseases. Curr Opin Pharmacol. 2019;49:60–70. https://doi.org/10.1016/j.coph.2019.09.006.
Elhoseeny MM, Rageh F, Rezk SM, Othman AAA. Frequency and risk factors of metabolic associated fatty liver disease among medical students in Egypt. Sci Rep. 2025;15(1):13470. https://doi.org/10.1038/s41598-025-95753-w.
Rensen SS, Slaats Y, Driessen A, Peutz-Kootstra CJ, Nijhuis J, Steffensen R, et al. Activation of the complement system in human nonalcoholic fatty liver disease. Hepatology. 2009;50(6):1809–17. https://doi.org/10.1002/hep.23228.
Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. New insights into the immune functions of complement. Nat Rev Immunol. 2019;19(8):503–16. https://doi.org/10.1038/s41577-019-0168-x.
Thorgersen EB, Barratt-Due A, Haugaa H, Harboe M, Pischke SE, Nilsson PH, et al. The role of complement in liver injury, regeneration, and transplantation. Hepatology. 2019;70(2):725–36. https://doi.org/10.1002/hep.30508.
Lazo M, Hernaez R, Bonekamp S, Kamel IR, Brancati FL, Guallar E, et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ. 2011;343:d6891. https://doi.org/10.1136/bmj.d6891.
Feng L, Zhao Y, Wang WL. Association between complement C3 and the prevalence of metabolic-associated fatty liver disease in a Chinese population: a cross-sectional study. BMJ Open. 2021;11(10):e051218. https://doi.org/10.1136/bmjopen-2021-051218.
Xu C, Chen Y, Xu L, Miao M, Li Y, Yu C. Serum complement C3 levels are associated with nonalcoholic fatty liver disease independently of metabolic features in Chinese population. Sci Rep. 2016;6:23279. https://doi.org/10.1038/srep23279.
Han J, Zhang X. Complement component C3: a novel biomarker participating in the pathogenesis of non-alcoholic fatty liver disease. Front Med. 2021;8:653293. https://doi.org/10.3389/fmed.2021.653293.
Guo Z, Fan X, Yao J, Tomlinson S, Yuan G, He S. The role of complement in nonalcoholic fatty liver disease. Front Immunol. 2022;13:1017467. https://doi.org/10.3389/fimmu.2022.1017467.
Brunt EM. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7(4):195–203. https://doi.org/10.1038/nrgastro.2010.21.
Malhi H, Gores GJ. Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28(4):360–9. https://doi.org/10.1055/s-0028-1091980.
Santiesteban-Lores LE, Carneiro MC, Isaac L, Bavia L. Complement system in alcohol-associated liver disease. Immunol Lett. 2021;236:37–50. https://doi.org/10.1016/j.imlet.2021.05.007.
Zhu C, Song H, Xu F, Yi W, Liu F, Liu X. Hepatitis B virus inhibits the expression of complement C3 and C4, in vitro and in vivo. Oncol Lett. 2018;15(5):7459–63. https://doi.org/10.3892/ol.2018.8223.
Li Y, Sha Y, Wang H, He L, Li L, Wen S, et al. Intracellular C3 prevents hepatic steatosis by promoting autophagy and very-low-density lipoprotein secretion. FASEB J. 2021;35(12):e22037. https://doi.org/10.1096/fj.202100856R.
Biewenga M, Farina Sarasqueta A, Tushuizen ME, de Jonge-Muller ESM, van Hoek B, Trouw LA. The role of complement activation in autoimmune liver disease. Autoimmun Rev. 2020;19(6):102534. https://doi.org/10.1016/j.autrev.2020.102534.
Zhuang L, Li Q, You W, Wen S, Chen T, Su J, et al. Complement C3 promotes islet beta-cell dedifferentiation by activating Wnt/beta-catenin pathway. iScience. 2024;27(10):111064. https://doi.org/10.1016/j.isci.2024.111064.
Spiga R, Marini MA, Mancuso E, Di Fatta C, Fuoco A, Perticone F, et al. Uric acid is associated with inflammatory biomarkers and induces inflammation via activating the NF-κB signaling pathway in HepG2 cells. Arterioscler Thromb Vasc Biol. 2017;37(6):1241–9. https://doi.org/10.1161/ATVBAHA.117.309128.
Chu CQ. Complement-targeted therapy for autoimmune diseases. Med Rev. 2023;3(6):521–5. https://doi.org/10.1515/mr-2023-0051.