| Title: | Novel subtypes of metabolic associated steatotic liver disease linked to clinical outcomes: implications for precision medicine |
| Journal: | Journal of Translational Medicine |
| Published: | 10 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40640848/ |
| DOI: | https://doi.org/10.1186/s12967-025-06670-5 |
| URL: | https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-025-06670-5 |
Publication 16841
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Abstract
Background & aimsAlthough metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with high multimorbidity and mortality, existing classification systems and risk prediction models largely ignore the heterogeneity of MASLD. Improved subtype definition could improve prediction of outcomes and inform new precision treatment strategies.MethodsWe analyzed individuals with MASLD from population-based electronic health record resource from UK Biobank (n = 125,197) and Health examinee dataset of Nanfang Hospital (n = 995). We identified subtypes with K-means clustering method. The Cox proportional hazard regression model analyzed the relationship between variables and MASLD-related complications.ResultsAfter identifying five clusters across seven clinical indicators which were age, body mass index, monocyte/lymphocyte ratio, aspartate aminotransferase, waist-hip ratio, low-density lipoprotein-cholesterol, and cholesterol, we labelled MASLD subtypes: (1) Metabolic-Dyslipidemia, (2) Younger, (3) Obesity, (4) Inflammatory, and (5) Hepatotoxic. Metabolic outcomes differed across these five subtypes. Hepatotoxic MASLD showed an increased risk of severe liver diseases compared to Metabolic-Dyslipidemia MASLD [HR = 13.9, 95% CI 10.7-18.1]. The extrahepatic complications were highest in Inflammatory MASLD. These two groups were defined as the high-risk group with higher health burden than other three groups, which classified as low-risk group. Differential single-nucleotide polymorphisms were concentrated on chromosomes 1 and 19 when comparing the high- and low-risk groups, and the annotated genes enrichment pathways were primarily related to lipid metabolism and transport. ConclusionsPatient subtypes derived by clinical indicators are a valuable addition to existing MASLD classification systems, which could provide a valuable tool to aid in selecting specific treatment approaches.Graphical Abstract</p>
25 Keywords
- Adult
- Age Factors
- Aspartate Aminotransferases
- Body Mass Index
- China
- Cholesterol
- Cluster Analysis
- Datasets as Topic
- Fatty Liver
- Female
- Genome-Wide Association Study
- Humans
- Lymphocyte Count
- Male
- Metabolic Diseases
- Middle Aged
- Monocytes
- Polymorphism, Single Nucleotide
- Precision Medicine
- Proportional Hazards Models
- Risk Factors
- Treatment Outcome
- UK Biobank
- United Kingdom
- Waist-Hip Ratio
15 Authors
- Chang Hong
- Sheng-xing Liang
- Ze-yang Li
- Rui-ning Li
- Hong-bo Zhu
- Mingfei He
- Hao Cui
- Jing-zhe He
- Yan Li
- Jia-ren Wang
- Xue-jing Zou
- Wen-yuan Li
- Lin Zeng
- Li Liu
- Lu-shan Xiao
1 Application
| Application ID | Title |
|---|---|
| 92668 | Development and validation of enhanced prediction models based on polygenic analysis and clinical factors for chronic diseases |
Enabling scientific discoveries that improve human health