Journal of Internal Medicine Concepts & Practice >
Multi-omics technologies in the study of clinical heterogeneity of metabolic associated fatty liver disease
Received date: 2026-02-20
Revised date: 2026-04-04
Accepted date: 2026-04-14
Online published: 2026-06-15
Copyright
Metabolic associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide and has become an important public health issue. MAFLD not only impairs liver function but is also closely associated with an increased risk of multi-system diseases, including cardiovascular disease, chronic kidney disease, and type 2 diabetes mellitus. However, current treatment for MAFLD still faces challenges such as a lack of effective drugs and significant limitations in drug efficacy. The core challenge lies in the high degree of clinical heterogeneity among MAFLD patients. This article systematically reviews the breakthrough research findings achieved by multi-omics technologies (including genome-wide association analysis, transcriptome sequencing, proteomics, and metabolomics) in deciphering the heterogeneity of MAFLD, and summarizes the MAFLD subtypes and their molecular mechanisms defined based on the above multi-omics characteristics, thereby providing a critical scientific basis for precision risk stratification and the development of personalized therapeutic targets for MAFLD patients.
DING Jingjing , CHAI Jin . Multi-omics technologies in the study of clinical heterogeneity of metabolic associated fatty liver disease[J]. Journal of Internal Medicine Concepts & Practice, 2026 , 21(02) : 119 -123 . DOI: 10.16138/j.1673-6087.2026.02.03
| [1] | Li QZ, Tan JX, Qin QZ, et al. Association between arterial stiffness and MASLD in US young adults: based on NHANES 2005-2018[J]. Am J Prev Cardiol,2025,22:101003. |
| [2] | Santhekadur PK, Kumar DP, Sanyal AJ. Preclinical models of non-alcoholic fatty liver disease[J]. J Hepatol,2018,68(2):230-237. |
| [3] | Kim KS, Hong S, Han K, et al. Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study[J]. BMJ,2024,384:e076388. |
| [4] | Moncho F, Benlloch S, Górriz JL. The impact of metabolic dysfunction-associated steatotic liver disease (MASH) on the high risk of cardiovascular disease in CKD: interconnections and management[J]. Clin Kidney J,2025,18(9):sfaf260. |
| [5] | Yoneda M, Yamamoto T, Honda Y, et al. Risk of cardiovascular disease in patients with fatty liver disease as defined from the metabolic dysfunction associated fatty liver disease or nonalcoholic fatty liver disease point of view: a retrospective nationwide claims database study in Japan[J]. J Gastroenterol,2021,56(11):1022-1032. |
| [6] | Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis[J]. N Engl J Med,2024,390(6):497-509. |
| [7] | Newsome PN, Sanyal AJ, Engebretsen KA, et al. Semaglutide 2.4 mg in participants with metabolic dysfunction-associated steatohepatitis:baseline characteristics and design of the phase 3 ESSENCE trial [J]. Aliment Pharmacol Ther, 2024, 60(11-12):1525-1533. |
| [8] | Lonardo A, Nascimbeni F, Ballestri S, et al. Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps[J]. Hepatology,2019,70(4):1457-1469. |
| [9] | Xu M, Gong R, Xie J, et al. Clinical characteristics of lean and non-lean non-alcoholic fatty liver disease: a cross-sectional study[J]. Nutr Metab (Lond),2025,22(1):40. |
| [10] | Nabi O, Lapidus N, Boursier J, et al. Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO study)[J]. Hepatology,2023,78(1):272-283. |
| [11] | Seko Y, Yamaguchi K, Shima T, et al. Clinical utility of genetic variants in PNPLA3 and TM6SF2 to predict liver-related events in metabolic dysfunction-associated steatotic liver disease[J]. Liver Int,2025,45(4):e16124. |
| [12] | Krawczyk M, Rau M, Schattenberg JM, et al. Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study[J]. J Lipid Res,2017,58(1):247-255. |
| [13] | Shi X, Wei X, Koo I, et al. Metabolomic analysis of the effects of chronic arsenic exposure in a mouse model of diet-induced fatty liver disease[J]. J Proteome Res,2014,13(2):547-554. |
| [14] | Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)[J]. Metabolism,2016,65(8):1038-1048. |
| [15] | Jamialahmadi O, De Vincentis A, Tavaglione F, et al. Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease[J]. Nat Med,2024,30(12):3614-3623. |
| [16] | Govaere O, Cockell S, Tiniakos D, et al. Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis[J]. Sci Transl Med,2020,12(572):eaba4448. |
| [17] | Wang B, Yu H, Gao J, et al. Machine learning deciphers the significance of mitochondrial regulators on the diagnosis and subtype classification in non-alcoholic fatty liver disease[J]. Heliyon,2024,10(9):e29860. |
| [18] | He J, Xiao C, Li C, et al. Integrative analysis of bulk and single-cell RNA sequencing data reveals distinct subtypes of MAFLD based on N1-methyladenosine regulator expression[J]. Liver Res,2023,7(2):145-155. |
| [19] | Ding J, Liu H, Zhang X, et al. Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population[J]. Sci Transl Med,2024,16(772):eadh9940. |
| [20] | Lu SC, Mato JM. S-adenosylmethionine in liver health, injury, and cancer[J]. Physiol Rev,2012,92(4):1515-1542. |
| [21] | Gautam J, Aggarwal H, Kumari D, et al. A methionine-choline-deficient diet induces nonalcoholic steatohepatitis and alters the lipidome, metabolome, and gut microbiome profile in the C57BL/6J mouse[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2024,1869(8):159545. |
| [22] | Drummer CIV, Saaoud F, Sun Y, et al. Hyperlipidemia may synergize with hypomethylation in establishing trained immunity and promoting inflammation in NASH and NAFLD[J]. J Immunol Res,2021,2021:3928323. |
| [23] | Alonso C, Fernández-Ramos D, Varela-Rey M, et al. Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis[J]. Gastroenterology,2017,152(6):1449-1461. |
| [24] | Martínez-Arranz I, Bruzzone C, Noureddin M, et al. Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles[J]. Hepatology,2022,76(4):1121-1134. |
/
| 〈 |
|
〉 |
