{
  "abstract": "Metabolic dysfunction-associated fatty liver disease (MAFLD) shows significant inter-patient heterogeneity, likely due to differences in the hepatic immune microenvironment. We aimed to identify clinically meaningful immunophenotypic subtypes based on quantitative expression of CD68, CD163, IL-6, and ZNF580. Liver biopsies from 19 patients with biopsy-proven MAFLD were analyzed. Immunohistochemical positive rates and counts for CD68, CD163, IL-6, and ZNF580 were quantified using digital image analysis. Hierarchical clustering identified patient subtypes. Clinical parameters, NAS, fibrosis stage, and ALT levels were compared across subtypes. Results : Three stable immunophenotypic subtypes were identified: Type M (macrophage-rich, high CD68/CD163, n = 7, 36.8%), Type I (inflammation-rich, high IL-6/ZNF580, n = 6, 31.6%), and Type D (immune-desert, low all markers, n = 6, 31.6%). NASs differed significantly ( p = 0.006, Kruskal-Wallis). Type D patients had the highest NAS (5.67 ± 0.82), significantly higher than Type I (3.83 ± 0.98, adj. p = 0.010) and Type M (4.14 ± 0.69, adj. p = 0.023). Fibrosis stage ( p = 0.542) and ALT levels ( p = 0.798) did not differ significantly. Intra-patient dominance analysis revealed macrophage-dominant (73.7%) and ZNF580-dominant (26.3%) cases, with no IL-6-dominant cases. Extreme case analysis showed that isolated high IL-6 (Patient 4) did not cause significant liver injury (NAS = 2, F0), whereas the immune-desert phenotype (Patient 23) presented with advanced bridging fibrosis (F3, NAS = 5) despite low marker expression. In this pilot cohort, our findings suggest that MAFLD may comprise three reproducible immunophenotypic subtypes with distinct histological activity but similar fibrosis burden. The immune-desert subtype is associated with high NAS despite low immune marker expression, suggesting immune-independent fibrogenic pathways. These findings provide a framework for precision immunophenotyping and subtype-targeted therapeutic strategies in MAFLD. However, due to the exploratory nature of this study and the small exploratory pilot cohort ( n = 19), our findings should be considered hypothesis-generating and require validation in larger cohorts.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Yuping Ding",
      "orcid": "0000-0001-5796-9558"
    },
    {
      "name": "Mingxia Chen"
    },
    {
      "name": "Fanhong Kong"
    },
    {
      "name": "Taotao liu"
    },
    {
      "name": "Li Zhu"
    },
    {
      "name": "Wencheng Zhang"
    },
    {
      "name": "Hong Yu"
    },
    {
      "name": "Shihai Xia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dhtx23gtptyg9.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-60628-1",
  "fulltext_url": null,
  "id": "dhtx23gtptyg9",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-60628-1",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Liver Disease Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7221183310",
  "pdf_url": "https://www.nature.com/articles/s41598-026-60628-1.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/dhtx23gtptyg9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:25Z",
      "native_id": "10.1038/s41598-026-60628-1",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-60628-1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Liver Disease Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Immunophenotypic subtypes of MAFLD distinct activity, comparable fibrosis",
  "title_text": "Immunophenotypic subtypes of MAFLD distinct activity, comparable fibrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:25Z",
  "url": "https://research.draconitic.com/paper/dhtx23gtptyg9",
  "venue": "Scientific Reports",
  "versions": []
}