Browsing by Subject "Primary biliary cholangitis"

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    Deconvolution analysis identified altered hepatic cell landscape in primary sclerosing cholangitis and primary biliary cholangitis
    (Frontiers Media, 2024-05-15) Pham, Hoang Nam; Pham, Linh; Sato, Keisaku; Medicine, School of Medicine
    Introduction: Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are characterized by ductular reaction, hepatic inflammation, and liver fibrosis. Hepatic cells are heterogeneous, and functional roles of different hepatic cell phenotypes are still not defined in the pathophysiology of cholangiopathies. Cell deconvolution analysis estimates cell fractions of different cell phenotypes in bulk transcriptome data, and CIBERSORTx is a powerful deconvolution method to estimate cell composition in microarray data. CIBERSORTx performs estimation based on the reference file, which is referred to as signature matrix, and allows users to create custom signature matrix to identify specific phenotypes. In the current study, we created two custom signature matrices using two single cell RNA sequencing data of hepatic cells and performed deconvolution for bulk microarray data of liver tissues including PSC and PBC patients. Methods: Custom signature matrix files were created using single-cell RNA sequencing data downloaded from GSE185477 and GSE115469. Custom signature matrices were validated for their deconvolution performance using validation data sets. Cell composition of each hepatic cell phenotype in the liver, which was identified in custom signature matrices, was calculated by CIBERSORTx and bulk RNA sequencing data of GSE159676. Deconvolution results were validated by analyzing marker expression for the cell phenotype in GSE159676 data. Results: CIBERSORTx and custom signature matrices showed comprehensive performance in estimation of population of various hepatic cell phenotypes. We identified increased population of large cholangiocytes in PSC and PBC livers, which is in agreement with previous studies referred to as ductular reaction, supporting the effectiveness and reliability of deconvolution analysis in this study. Interestingly, we identified decreased population of small cholangiocytes, periportal hepatocytes, and interzonal hepatocytes in PSC and PBC liver tissues compared to healthy livers. Discussion: Although further studies are required to elucidate the roles of these hepatic cell phenotypes in cholestatic liver injury, our approach provides important implications that cell functions may differ depending on phenotypes, even in the same cell type during liver injury. Deconvolution analysis using CIBERSORTx could provide a novel approach for studies of specific hepatic cell phenotypes in liver diseases.
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    Histopathological Evaluation of Recurrent Primary Biliary Cholangitis after Liver Transplantation
    (XHP, 2022) Weldemichael, Wegahta; Zhang, Dongwei; Lin, Jingmei; Pathology and Laboratory Medicine, School of Medicine
    The pathomorphological features of primary biliary cholangitis (PBC) is well-established. However, the distinction between PBC recurrence, and T cell-mediated rejection or chronic rejection remains as a challenge for pathologists. Due to the overlapping morphology, correct diagnosis requires a highly specific discrimination. Accurate diagnosis plays an essential role in patient management since different therapeutic strategies are used. This review focused on the role of pathologists in evaluating the allograft liver biopsy of patients with PBC as the leading cause of native liver cirrhosis. Furthermore, the clinicopathologic features of recurrent PBC, and T cell-mediated rejection or chronic rejection were discussed in detail, with emphasis in distinguishing the histopathology, morphologic variant, and diagnostic pitfalls.