[1593] The Role of Oval Cell Activation and Periportal Ductular Reaction Presence in Two Different Models of Experimental Cirrhosis

C Kalogeropoulou, I Tsota, P Zabakis, D Kardamakis, T Petsas, AC Tsamandas. University of Patras, Patras, Greece

Background: Oval cells (OC) are liver stem cells involved in the progress of liver disease and hepatocellular carcinoma development. This study investigates the potential correlation of OC activation and the resultant periportal ductular reaction (PDR), and impaired liver cell replication, in experimental liver fibrosis.
Design: The study comprised 102 male Wistar rats divided in 3 groups: A (n=6) controls, B (n=48):CCl4 injection (intraperitoneally 2ml/kg/BW-1:1 vol in corn oil twice weekly), C (n=48): thioacetamide administration in drinking water (300 mg TAA/L) for 3 months. In group B, rats were sacrificed at 4, 8, 12 weeks and in group C, at 1, 2 and 3 months. At all times, liver tissues were obtained and were stained with antibodies to CK19, LCA, CD34, and p21. Cells with features of OC that were CK19+/LCA(-)/CD34(-) were scored. PDR was defined according to standard reference (Roskams T, Hepatology 39:1739, 2004). The presence of OC was also determined by quantification of AFPmRNA (RT-PCR method). PDR was quantified as % of biopsy area.
Results: The table lists the results. Statistical analysis revealed significant correlation between a) OC with fibrosis (group B: p=0.0021, group C: p=0.0032), b) PDR and fibrosis (group B: p=0.0012, group C: p=0.0019). Impaired hepatocyte replication (%p21+ cells) was independently associated with a) %OC (group B: p=0.0028, group C: p=0.0041) and b) PDR (group B: p =0.0057, group C: p =0.0075). Multivariate analysis showed that PDR is independent factor for the prediction of fibrosis.

Table: OC expression and PDR presence in the different groups

Groups	CK19	AFPmRNA	PDR
A	2.7±0.4	2.5±0.7	1.6±0.09
B1	15.6±4.8c	16.8±6.4d	14.3±5.7e
B2	36.1±7.2c	37.5±8.3d	35.7±7.4e
B3	54.8±7.7c	56.4±8.9d	49.6±6.4e
C1	14.2±5.6h	17.3±5.2i	16.4±5.8j
C2	36.9±8.5h	37.8±7.4i	35.9±8.1j
C3	59.5±9.4h	58.3±6.8i	54.3±8.5j

^{a, c, d, e, f, h, i, j} : p<0.001 and ^{b, g} : p<0.05 when compared to controls.


Conclusions: This study demonstrates that in experimental liver fibrosis (irrespective of the model used for cirrhosis induction), OC activation and PDR degree, strongly correlates with the progress of liver fibrosis. 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.
Category: Liver & Pancreas

Monday, March 22, 2010 1:00 PM

Poster Session II # 177, Monday Afternoon