Pathological significance of intranuclear structures in liver biopsy samples

Abstract Aim Glycogenated nuclei (GN) are glycogen deposits within the nuclei and are a frequent pathological finding in metabolic dysfunction‐associated steatotic liver disease. This study aimed to investigate the relationship between GN and two morphologically distinct types of intranuclear lipid droplets in liver biopsy specimens and to explore their respective pathological significance. Methods We analyzed 135 liver biopsy specimens. A portion of the liver biopsy specimen was examined using transmission electron microscopy (TEM) to investigate intranuclear lipid droplets in hepatocytes. Nuclear inclusion bodies with clear boundaries and unstained areas on hematoxylin and eosin staining were identified as nuclear glycogen. Results TEM revealed nucleoplasmic lipid droplets (nLD) in 65% of liver biopsy specimens and invagination of cytoplasmic lipid droplets into the nucleus in 30% of specimens. In contrast, light microscopy detected GN in 82% of specimens. No significant correlations were observed between the frequencies of the two types of intranuclear lipid droplets and nuclear glycogen levels. A significant positive correlation was observed between the frequency of nLD and transaminase levels. Glycogenated nuclei were frequently observed in liver biopsy specimens from patients with MASLD; however, their frequency did not significantly correlate with the degree of hepatic steatosis. Instead, a significant positive correlation was observed between nuclear glycogen and blood HbA1c levels. Conclusions The two types of intranuclear lipid droplets and nuclear glycogen observed in liver biopsy specimens showed no significant correlation in their formation frequencies, suggesting that they possess distinct pathological significance.