Pathological changes and iNOS expression in portal vein and hepatic artery of patients with liver cirrhosis and portal hypertension

Objective: To investigate pathological alterations in morphologies of the portal vein, hepatic artery, and hepatic vein in patients with liver cirrhosis and portal hypertension (PHT), to study inducible nitric oxide synthase (iNOS) expression in the hepatic artery wall, and to explore roles of iNOS in pathogenetic mechanisms of portal hypertensive vasculopathy. Methods: Sections of the portal vein, hepatic artery, and left liver vein were obtained from 11 noncirrhotic patients during hepatectomy and 24 patients with liver cirrhosis and PHT during liver transplantation. Specimens were observed by optical microscopy. Expression of iNOS in liver artery walls was analyzed by immunohistochemistry. Results: In portal veins of cirrhotic patients, we found proliferative intima, extensive thrombi adhering to the venous walls, and thickened muscle fibers of veins with increased extracellular matrix. Thrombi mimicked arteriosclerotic plaques and were accompanied by smooth muscle cell hypertrophy. Internal elastic membrane and medial elastic fibers of the hepatic artery wall were broken and degenerated. Few changes in the hepatic vein were observed. Positive staining for iNOS was seen in the smooth muscle cell cytoplasm. Furthermore, iNOS activity was elevated in cirrhotic compared to noncirrhotic patients (P < 0.01). Conclusion: PHT may be complicated by hepatic arterial and portal vein vasculopathy. There may be an interactive relationship among PHT, hyperdynamic splanchnic circulation, and splanchnic vasculopathy in the pathogenesis of PHT.