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Intraparenchymal isolated bile ductules (IIBDs) are occasionally recognizable in liver specimens, but their characteristics remain poorly understood. Therefore, we (2 pathologists) attempted to identify IIBDs in 81 hematoxylin and eosin-stained needle biopsy specimens of the liver, and examined the interobserver variation and their clinicopathologic features. Aberrant cytokeratin 7 (CK7) expressions of hepatocytes, known to represent hepatic progenitor cell (HPC) activation, were also evaluated. In each specimen, the mean number of IIBDs counted by us was divided by the number of portal areas, which was defined as the IIBD score. Both pathologists detected IIBDs in 53 specimens (65.4%), indicating that they are not rare. Observed agreement was obtained in 81.5%, and the kappa statistic indicated moderate agreement (kappa: 0.515). Higher IIBD score was closely associated with a higher degree of hepatocytic CK7 expression in all areas (P=0.012), periportal areas (P=0.007), and pericentrilobular vein (CV) areas (P=0.032), but not with age, gender, increased serum levels of liver dysfunction tests, or hepatic steatosis. Ductular reaction was also associated with hepatocytic CK7 expression in all areas (P=0.004), periportal areas (P=0.024), and peri-CV areas (P=0.031). However, there was not a relevant relationship between higher IIBD score and a severe degree of ductular reaction. In non-alcoholic steatohepatitis (NASH) cases, significant IIBD score was correlated with grading score (P=0.043), but not with fibrosis staging score. In viral hepatitis cases, it was not associated with grading or staging score. These results suggested that the development of IIBD can highlight HPC activation, but might be independent of periportal HPCs, also known as “periportal niches”. The presence of IIBDs would be due in part to a hepatic necro-inflammatory state in some conditions, such as NASH.

Intraparenchymal Isolated Bile Ductules in the Needle Biopsy Specimens of the Liver: An Interobserver Variation and Clinicopathological Study