Aberrant von Willebrand Factor Expression of Sinusoidal Endothelial Cells and Quiescence of Hepatic Stellate Cells in Nodular Regenerative Hyperplasia and Obliterative Portal Venopathy

Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV), entities that comprise idiopathic noncirrhotic portal hypertension (INCPH) are under-recognized diseases of uncertain etiology and the diagnosis can be easily missed on liver biopsy. The expression of CD34 and von Willebrand factor (vWF) in sinusoidal endothelial cells (LSEC) and alpha-smooth muscle actin (ASMA) in hepatic stellate cells (HSC) is unknown in NRH and OPV. We sought to investigate the pathogenesis and potential immunomarkers that might aid in making the diagnosis of NRH and OPV. Immunohistochemical (IHC) staining for CD34, vWF and ASMA was performed in clinically and histologically well-characterized NRH (n=15) and OPV (n=47) liver specimens. Among the 47 OPV cases, 37 (78.7%) had concurrent features of NRH. CD34+ staining was mainly confined to small vessels in the portal tracts and LSECs in periportal areas, a finding similar to that in non-NRH/OPV livers. However, expression of vWF in LSECs was positive in the compressed sinusoids of NRH, and in a patchy or geographic pattern, particularly prominent in the perivenular areas and dilated sinusoids of OPV cases. HSCs were negative for ASMA in all NRH and OPV cases. Our findings indicate that NRH may be subtle but is a common concurrent morphologic feature in OPV. The aberrant expression of vWF in LSECs suggests that endothelial injury may play role in the pathogenesis, which may thus aid in the recognition and diagnosis of NRH and OPV, particularly when confronted with otherwise apparent normal liver histology on needle biopsy.