Background: Neutrophilic cholangitis (NC) and reactive hepatitis (RH) represent different forms of liver inflammation thought to have different etiologies and hence management approaches. While classic cases are readily distinguishable, mild or early stage NC may present with only non-specific RH changes, making accurate diagnosis challenging.
Objective: To compare gene expression in liver tissue with histologically confirmed NC and RH and control samples using a commercially available canine Immunology and Oncology Nanostring™ panel, with the aim of identifying distinct molecular signatures that would support differing etiologies and pathogeneses between these conditions.
Animals: 36 client-owned dogs.
Methods: Archived samples from 14 NC, 13 RH, and 6 control cases were included in the study. For each, total RNA was purified. The nCounter Digital Analyser quantified the target RNA within the Nanostring™ panel. Raw data was normalized within nSolver and differentially expressed (DE) genes identified. Normalized data was analyzed using R and ingenuity pathway analysis.
Results: NC and RH samples clustered separately following Principal Components Analysis, the former most closely aligned with control samples. Comparing the NC and RH groups, we identified 136 DE genes (p < 0.05). Following Bonferroni correction, 15 genes remained significant. Notably, the majority of inflammatory genes were upregulated in the NC group. Top regulators of the DE genes included, LPS, TNF, and IL4.
Conclusions and clinical importance: NC and RH display distinct transcriptional signatures, providing molecular evidence of their differing etiopathogeneses. These results support a key role of bacteria/bacterial products as drivers of NC but not RH.
