Aberrant von Willebrand Factor Expression of Sinusoidal Endothelial Cells and Quiescence of Hepatic Stellate Cells Help in the Diagnosis of Hepatoportal Sclerosis
Xuchen Zhang, Thomas D Schiano, Swan N Thung, Stephen C Ward, M Isabel Fiel. The Mount Sinai Medical Center, New York, NY
Background: Hepatoportal sclerosis (HPS) is an under-recognized disease of uncertain etiology and the diagnosis can be easily missed on needle liver biopsy. HPS is characterized by portal fibrosis and obliteration of small and medium branches of the portal vein, resulting in the development of portal hypertension, and its sequelae. A recent FDA advisory about the use of anti-retroviral agents (ddI) as a cause of non-cirrhotic portal hypertension in HIV+ individuals has been issued. Liver sinusoidal endothelial cells (SEC) are unique because expression of CD34 and von Willebrand factor (vWF) are only found in periportal areas. Hepatic stellate cells (HSC) when activated lead to liver fibrosis and their activation as characterized by alpha smooth muscle actin (ASMA) expression, is unknown in HPS. We sought to find immunomarkers that might help in making the diagnosis of HPS.
Design: Immunohistochemical (IHC) staining for CD34, vWF and ASMA was performed and evaluated in 10 (3 core biopsies and 7 explants) clinically and histologically well-characterized HPS liver specimens.
Results: As is typical for HPS, the pathological findings were heterogeneous, but all specimens showed various degrees of dense portal fibrosis and obliterated portal veins. Abnormally dilated channels were present in the vicinity of portal areas. CD34 (+) staining was mainly confined to small vessels in the portal tracts and SECs at periportal areas, a similar finding in normal livers. Unlike CD34, however, SEC expression of vWF was (+) in a patchy or geographic pattern and was particularly prominent in perivenular areas. HSCs were not activated as defined by totally absent staining for ASMA in all HPS cases.
Conclusions: In this study, we found that immunostaining for CD34, vWF and ASMA may aid in the diagnosis of HPS. CD34 and vWF are commonly used endothelial markers; vWF mediates platelet adhesion to the subendothelium at sites of vascular injury as well as binding to and stabilizing factor VIII in the circulation. The current study shows a patchy and geographic SEC(+) pattern for vWF, suggesting that endothelial injury plays a role in the pathogenesis of HPS. HSCs are not activated in HPS suggesting that these cells are not directly involved in the pathogenesis of HPS. The aberrant expression of vWF may thus aid in the diagnosis of HPS, particularly when confronted with otherwise apparent normal liver histology on needle biopsy.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 241, Wednesday Morning