Histogenesis of the human fetal liver: evaluation of hematopoietic to hepatocytic lineage transition markers across gestation.

Abstract

The human fetal liver undergoes sequential structural and functional maturation during gestation, serving initially as the primary hematopoietic organ before transitioning to a metabolically active gland. However, limited studies have correlated histological development with lineage-specific immunohistochemical markers to determine the period of shift in hematopoietic to hepatocytic functionality. Thirty human fetal livers from gestation 12 to 36 weeks, collected at AIIMS Nagpur between March 2024 and December 2025, were studied using a cross-sectional analytical design. Hematopoietic and hepatocytic lineage immunomarkers such as CD34, alpha-fetoprotein (AFP), epithelial cell adhesion molecule (EpCAM), and cytokeratin 19 (CK19) were analyzed descriptively and inferentially to determine the timing of lineage shift. Both descriptive and inferential statistics were done to determine the significance of the study findings. Progressive maturation of hepatic architecture with advancing gestational age showed statistical significance (P<0.001). Special staining confirmed structural and functional maturity with advancing gestational age. Prominent hematopoietic clusters observed in early gestation showed significant decline toward the third trimester. CD34 expression demonstrated a strong negative correlation with gestational age (r=-0.8337, P<0.001), whereas CK19 showed a moderately positive correlation (r=0.4326, P=0.017). EpCAM expression peaked during the second trimester and declined thereafter (r=-0.3834, P=0.0365). AFP expression remained consistently strong across all gestational ages. The human fetal liver demonstrates coordinated histological and immunophenotypic maturation, with a critical transition from hematopoietic to hepatobiliary predominance occurring between 24 and 28 weeks of gestation. These findings provide valuable insights into fetal liver histogenesis and may support future applications in regenerative medicine and stem cell research.