Hepatic progenitor cell activation and ductular reaction in metabolic dysfunction-associated steatotic liver disease (MASLD): Indicators for disease activity and the degree of fibrosis: The pilot study

Metabolic dysfunction-associated steatotic liver disease (MASLD) spectrum encompasses steatosis, metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis and metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma. We evaluated the histomorphologic findings, portal-periportal biliary epithelial cell changes, and factors that may be associated with the degree of fibrosis in liver biopsies of MASLD patients. Hematoxylin-eosin, masson-trichrome, keratin7, keratin19, CD34, and glutamine synthetase-stained biopsies of 34 patients and 10 healthy liver donors (as controls) were retrospectively analyzed. Lobular inflammation was significantly correlated to the ballooning degeneration (P = .023), portal inflammation (P = .003), ductular reaction (DR) grade (P = .027), and the degree of fibrosis (P = .003). Ballooning degeneration (P = .004), and NAS (P = .008) were significantly related to the degree of fibrosis. Portal inflammation had a significant relationship with both DR grade (P < .001) and the degree of fibrosis (P = .002). The presence of hepatic progenitor cells (HPCs) was related to NAS (P = .005) and correlated with the DR grade (P = .002) and the degree of fibrosis (P = .038). Both DR (P < .001) and biliary metaplasia (P = .024) were significantly correlated with the degree of fibrosis. In multivariate analysis, biliary metaplasia (P = .015) and DR (P = .02) were found to be independent factors related to degree of fibrosis. Our results showed that HPC and DR were closely associated with disease activity and degree of fibrosis and might be good indicators of disease progression in MASLD. As pathologists, we might integrate the degree of HPCs and the grade of DR in our pathology reports as these findings might contribute to the disease progression risk categorization of the patients.