Early Hepatic Stellate Cell Activation in Fibrosing Cholestatic Hepatitis
CP Jenkins, LR Dixon. University of Florida, Gainesville, FL
Background: Recurrent hepatitis C (RHCV) after liver transplantation (post-LT) is almost universal, and in some patients takes an aggressive course characterized histologically by pericellular/sinusoidal fibrosis and cholestasis, known as fibrosing cholestatic hepatitis (FCH). FCH progresses rapidly often resulting in graft failure within a few months. The hepatic stellate cell (HSC) is the predominant source of extracellular matrix and type I collagen in the liver. Smooth muscle actin (SMA) immunoreactivity is present in HSCs, and early activation of portal HSCs in post-LT recipients has been shown to predict subsequent fibrosis in RHCV. The degree of HSC activation in FCH has not been studied, and may prove useful in establishing a diagnosis of FCH as well as differentiating FCH from a severe, but more slowly progressive, RHCV.
Design: Subjects were selected from an established database of post-LT hepatitis C patients. Subject groups included patients who developed FCH (n=8) and those with severe RHCV (fibrosis score of >/=3 of 6 at 2 years post-LT, n=6). Control subjects were selected from this same patient pool, and consisted of stable post-LT patients (fibrosis score of </=2 of 6 at 2 years post-LT, n=5). Immunohistochemistry was performed on paraffin sections of formalin-fixed tissue using the ABC/peroxidase method with SMA on biopsies at 1 week and 4 months post-LT. Staining patterns and intensity were recorded and compared between study groups.
Results: SMA reactivity at 1 week post-LT was severely increased in the majority (63%, n=5) of FCH and in all severe RHCV patients. At 4 months post-LT the SMA reactivity was also severely increased in the majority (88%, n=7) of FCH and severe RHCV (67%, n=4) patients. Stable post-LT patients exhibited none (n=1) to mild (n=4) SMA reactivity at 1 week post-LT and none (n=1) to moderate (n=3) reactivity at 4 months post-LT. Four FCH patients expired within 10 months post-LT, all having severe SMA reactivity at 4 months post-LT.
Conclusions: The FCH and severe RHCV patients had greater SMA reactivity/HSC activity at both 1 week and 4 months post-LT than stable post-LT patients. The prevalence of severe HSC activation at 4 months post-LT was greater in the FCH patients than in RHCV patients allowing possible means to differentiate the two. Activation of portal HSCs at 1 week and 4 months in post-LT hepatitis C patients is a specific marker for progressive fibrosis to distinguish those who will have either an aggressive RHCV or FCH course and may help to select patients who would benefit from early aggressive therapy.
Category: Liver & Pancreas
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 207, Monday Morning