The contribution of metabolomics to the histopathologic diagnosis of hepatitis C and autoimmune liver diseases


José Ramón Vizcaíno 
Anatomical Pathologists 

José Ramón Vizcaíno is an attending physician of Pathological Anatomy at ULS de Santo António.
He completed his PhD in Health Sciences at the University of Murcia in Spain in December 2022 under the supervision of Professor José Antonio Pons Miñano.

 

What made you choose this study topic?

The histopathologic diagnosis of hepatitis C (HCV) and autoimmune liver diseases such as primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) requires the integration of biochemical, serologic, immunologic, and molecular data. This is because there are no pathognomonic morphologic features in histologic biopsy that allow a definitive diagnosis. In the absence of data favoring one entity, biopsy is an essential element to aid in the diagnosis, which will always be a presumptive one.

 

What are the study's main findings?

For this study, 62 patients were ed and divided into four s: control (n=13); PBC (n=11); HCV (n=21); and AIH (n=17). The metabolite extraction product paraffin-embedded liver biopsy tissue analyzed by HPLC-MS/MS yielded 95 metabolites, of which 53 met the imposed precision criterion (35%). The predictive models generated with these 53 metabolites for the different diagnostic s showed a good discriminatory ability for control vs. HCV (area under the curve [AUC]=0.88), control vs. HAI (AUC=0.81), and HCV vs. CBP (AUC=0.88), and an excellent discriminatory ability for control vs. AIH (AUC=0.96), HCV vs. CBP (AUC=0.97), and AIH vs.  CBP (AUC=0.92). The analysis of metabolic pathways the modules generated in the perturbed correlation network of the different diagnostic s suggested a disruption of carbohydrate metabolism in the control vs. HCV and HCV vs. PBC s, of amino acid metabolism in the HCV vs. AIH and AIH vs. PBC s, of nucleotide metabolism in the HCV vs. AIH, AIH vs. PBC, and control vs. PBC s, and of energy metabolism in the control vs. PBC . The low discriminatory ability of the morphological variables did not contribute to improve the discriminatory power of the models generated with the metabolites. Overall, it was not possible to identify a set of metabolites discriminatory enough to build a model for predicting the degree of fibrosis and necroinflammatory activity.

 

What is the main conclusion of the study?

In conclusion, metabolomics may provide the basis for a highly relevant complementary technique for the histopathologic diagnosis of hepatitis C and autoimmune hepatopathies. Histologic examination of the biopsy remains crucial to assess fibrosis and necroinflammatory activity.