Keratin 7 staining reveals disease progression markers in fatty liver disease biopsies
Quantitative analysis of K7-positive cell populations in 36 MASLD liver biopsies found that ductular reaction density increased significantly with fibrosis stage, while progenitor cells peaked at grade 3 necro-inflammatory activity. Intermediate hepatocytes were notably higher in MASH versus simple steatosis. The study suggests that K7 immunohistochemistry could refine MASLD diagnosis and improve patient stratification in clinical trials beyond routine histological scoring.
The original study
Keratin 7 immunohistochemistry reveals patterns of cell populations in liver biopsies from patients with MASLD.
- Authors
- Ducor L, Fraga M, Manco R, Mdawar-Bailly E, Vieira J, Sempoux C, et al.
- Journal
- Journal of clinical pathology
- PMID
- 41876217
Original abstract
AIMS: Metabolic-associated steatotic liver disease (MASLD), which encompasses metabolic associated steatotic liver (MASL) and metabolic-associated steatohepatitis (MASH), is the most common chronic liver disorder worldwide. Fibrosis stage remains the most dependable histological predictor of prognosis; however, routine stains do not fully capture regenerative and injury-related processes. Keratin 7 (K7) immunohistochemistry highlights bile ducts (BDs), ductular reaction (DR), hepatic progenitor cells (PCs) and intermediate hepatocytes (IHs), all of which are involved in regeneration and fibrogenesis. This study aims to quantify K7-positive cell populations across histological stages of MASLD to enhance disease characterisation and evaluate the diagnostic value of K7 immunohistochemistry in this setting. METHODS: Archived liver biopsies from a clinically well-characterised cohort of 36 patients (17 MASH, 19 MASL) were stained for K7, digitised and analysed using QuPath with manual expert review. K7-positive structures were classified into BD, DR, PC or IH, with over 10 000 objects quantified. Profile densities and portal tract normalised ratios were calculated and correlated with clinical, biochemical and histological grading and staging by the Steatosis Activity and Fibrosis score. RESULTS: PC showed the strongest association with necro-inflammatory activity, peaking at grade 3. DR density increased significantly with fibrosis, supporting its role as an early marker of disease progression. IH was notably higher in MASH than in MASL, resulting in higher IH/DR ratios. CONCLUSION: Specific quantitation of K7-positive cell populations can refine the diagnosis of MASLD and complement routine scoring in clinical trials to improve patient stratification.