Immunohistochemical Profile of the Pulmonary Vasculature in Subjects with Portopulmonary Hypertension: an Autopsy Study

Portopulmonary hypertension (POPH) is a complication of cirrhosis that results in right ventricular failure and death. The objective of this autopsy investigation was to compare pulmonary arterial receptors in the lung of subjects with POPH and those with cirrhosis lacking pulmonary vascular complications. Autopsy records of 824 subjects with cirrhosis were reviewed to identify pulmonary arterial vasculopathy and microscopic confirmation of the histopathologic findings. Lung sections from paraffin embedded blocks were prepared and immunohistochemical stains performed for CD31, CD34, endothelin A (ET-A), endothelin B (ET- B), estrogen alpha (ER-α), estrogen beta (ER-β), and vascular endothelial growth factor (VEGF) for POPH subjects and control subjects with cirrhosis without pulmonary vasculopathy. Pulmonary vascular immunohistochemical reactivity in the POPH and control groups were compared. POPH was identified in 29 individuals with intimal hyperplasia (93%), medial hypertrophy (96%), and plexiform lesions (72.4%). Immunohistochemical staining for ET-A revealed positive reactivity in 40% of the POPH group and 13% of the control group (NS). ET-B reactivity in the pulmonary endothelium and smooth muscle was identified in all POPH subjects and control group. VEGF reactivity was identified in the endothelium in all the POPH group compared with 33% of the control group (p=0.0002). ER-β reactivity was observed in four subjects (26.6%) in the POPH group while none in the control group. POPH was found in 3.5% of autopsies with the pulmonary vasculature immunohistochemical profile demonstrating endothelial and smooth muscle reactivity for endothelin, ER-β and VEGF.