The Role of Hepatic Progenitor Cell Activation and Periportal Ductular Reaction Presence in Chronic Hepatitis C and B. A Clinicopathologic Study
A Tsamandas, K Thomopoulos, I Syrokosta, D Dimitropoulou, C Karatza, C Gogos. Univ. of Patras, Patras, Greece
Background: Hepatic progenitor cells (HPC) are liver stem cells that involved in the progress of liver disease. This study investigates the potential correlation of HPC activation and the resultant periportal ductular reaction (PDR) with disease severity and response to treatment, and impaired liver cell replication, in patients with HCV and HBV.
Design: The study included 284 liver biopsies obtained from 142 patients with HCV(n=77) and HBV(n=65). All patients received therapy and assigned as: [HCV:responders(A=29), non-responders(B=29), relapsers(C=19)], [HBV:responders(negative HBVDNA and LFTs normalization) (D=40) and non-responders (E=25). 77 HCV/65 HBV biopsies were obtained before treatment (A1/ B1/C1/D1/E1) and the remaining after (A2/B2/C2/D2/E2). Paraffin sections were stained with antibodies to CK7, LCA, CD34, and p21. Cells with features of HPC (Roskams T, Hepatology 39:1739, 2004) that were CK7+/LCA(-)/CD34(-) were scored. The same reference was used to define PDR. The presence of HPC was also determined by gene analysis for AFPmRNA, performed on microdissected liver tissue samples. PDR was quantified as % of biopsy area.
Results: The table lists the results. Statistical analysis revealed significant correlation between a) HPC with fibrosis (HCV: p=0.0028, HBV: p=0.0041) and inflammation (HCV: p=0.0035, HBV: p=0.0052), b) PDR and fibrosis (HCV: p=0.0017, HBV: p=0.0024). Impaired hepatocyte replication (%p21+ cells) was independently associated with a) %HPC (HCV: p=0.0031, HBV: p=0.0048) and b) PDR (HCV: p =0.0042, HBV: p =0.0061). Multivariate analysis showed that PDR is independent factor for the prediction of fibrosis.
Conclusions: This study shows that in HCV and HBV cases, HPC activation and PDR degree, are significantly decreased in patients with response to treatment, implying that they are strongly correlated with disease severity. The fact that these factors are associated with impaired hepatocyte replication implies the presence of an alternative pathogenetic pathway during liver regeneration that leads to PDR and progressive liver fibrosis, with consequent liver failure.
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Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 154, Tuesday Morning