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Histopathologic and immunophenotypic features distinguishing recurrent primary biliary cholangitis from liver
Nigar Anjuman Khurram1, Alexander Miller2, Neha Varshney3
1University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Background:
Recurrent primary biliary cholangitis (rPBC) is a major cause of post-transplant cholangiopathy and frequently mimics allograft rejection on liver biopsy, creating a common diagnostic challenge with important therapeutic implications. However, the pathologic alterations distinguishing these entities, particularly within the biliary and progenitor compartments, remain incompletely defined.
Methods:
A retrospective single-center study evaluated 54 liver allograft biopsies: 29 rPBC biopsies (15 patients) and 25 rejection biopsies (22 patients). Biopsies were assessed using the Banff liver allograft schema with semiquantitative evaluation of biliary features. Immunohistochemistry for CK7, CK19, CD1a, and S100, together with the canal-of-Hering loss (CoH-L) ratio, evaluated ductular remodeling and progenitor compartment integrity. Because serial biopsies occurred in both groups, robustness was assessed by repeated one-biopsy-per-patient resampling.
Results:
Ductular reaction favored rPBC (p < 0.001; AUC 0.748) and venous endothelial inflammation favored rejection (p = 0.002; AUC 0.726); both were significant in every resampling draw. Florid duct lesions were identified only in rPBC (6/29 vs 0/25, p = 0.025) but were absent from most rPBC biopsies. CK7 quantification (p = 0.032) and the CoH-L ratio (p = 0.010) were greater in rPBC but less robust to resampling, whereas S100-positive dendritic cells did not differ significantly (6/27 vs 1/25, p = 0.101). Total bilirubin (AUC 0.786) discriminated better than any single tissue feature.
Conclusions:
rPBC was associated with greater biliary and progenitor-compartment remodeling than rejection, although later biopsy timing in rPBC means these differences may partly reflect graft chronicity. Ductular reaction was the most sampling-robust biliary feature, while florid duct lesions favored rPBC when present. CK7 quantification, CoH-L, and S100-positive dendritic cells provide complementary, hypothesis-generating signals requiring validation in larger independent cohorts.
