Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis

作者：Shan Shan, Xinyan Zhao, Michelle A. Wood, Doudou Hu, Liwei Liu, Beining Qi, Jianbo Jian, Ping Wang, Wenjuan Lv, Chunhong Hu · 发表于：The Journal of Pathology · 年份：2024 · DOI：10.1002/path.6273 · 被引用次数：8 · 研究领域：Liver Disease and Transplantation、Liver Disease Diagnosis and Treatment、Pediatric Hepatobiliary Diseases and Treatments

Abstract The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two‐dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B‐related cirrhosis (Hep‐B‐cirrhosis, n = 35). Then, three‐dimensional (3D) OPV was measured by X‐ray phase‐contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl 4 ) administration, representing biliary cirrhosis and post‐necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep‐B‐cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl 4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl 4 model. With the proliferation of bile ducts, portal venules were co...