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Analysis Of The intrahepatic ductular reaction and progenitor cell responses in hepatitis C virus recurrence Post-Liver transplantation

Prakoso, E., Tirnitz-Parker, J.E.E., Clouston, A.D., Kayali, Z., Lee, A., Gan, E.K., Ramm, G.A., Kench, J.G., Bowen, D.G., Olynyk, J.K., McCaughan, G.W. and Shackel, N.A. (2014) Analysis Of The intrahepatic ductular reaction and progenitor cell responses in hepatitis C virus recurrence Post-Liver transplantation. Liver Transplantation, 20 (12). pp. 1508-1519.

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Background: Fibrosis in liver with hepatitis C virus (HCV) recurrence post-liver transplantation (LT) can be rapidly progressive and the mechanisms underlying this process are poorly understood. In liver with HCV infection in the non-LT setting, there is a significant relationship between the development of structures known as the ductular reaction (DR), hepatic progenitor cells (HPCs) and fibrosis. In this study, we have characterized the DR, HPCs and fibrosis associated with HCV recurrence post-LT.

Methods: Immunohistochemistry and confocal microscopy were used to characterize the DR, HPC and fibrosis in liver biopsy specimens. Key findings were confirmed in a separate independent cohort.

Results: The initial characterization cohort had 194 biopsy samples from 105 individuals with HCV recurrence post-LT. The immunophenotype, morphology and location of the DR was consistent with an HPC origin. The DR correlated with intrahepatic fibrosis (rs=0.529, p<0.001) and numbers of activated hepatic stellate cells (HSCs, rs=0.446, p<0.001). There was an early occurrence of hepatocyte replicative arrest and increased hepatocyte proliferation that correlated with the DR (rs=0.295, p<0.001). Replicative arrest preceded hepatocyte proliferation in early stage injury. Hepatocyte proliferation decreased with advanced fibrosis, in contrast the extent of the DR and numbers of activated HSCs continued to increase. In the second cohort of 37 individuals, the DR and numbers of HPCs similarly correlated with fibrosis and inflammation post-LT.

Conclusions: This is the first characterization of the DR in HCV-associated liver injury post-LT. There was a significant correlation between the DR and the development of progressive fibrosis in HCV recurrence. These results suggest a pivotal role for both the DR and HPC responses in the aggressive fibrosis seen with HCV recurrence post-LT. Liver Transpl , 2014

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Wiley
Copyright: © 2014 American Association for the Study of Liver Diseases
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