Distribution of hepatic nerve fibers in liver diseases

Autonomic hyperactivity with increased cardiac output and other manifestations occurs in patients with both cirrhosis and noncirrhotic portal hypertension. The role of the disordered hepatic autonomic innervation in the mediation of these abnormalities is unknown. We have studied the hepatic nerve network and associated extracellular matrix proteins in patients with portal hypertension (alcoholic cirrhosis, extrahepatic portal vein obstruction, idiopathic portal hypertension), and in patients without portal hypertension (alcoholic hepatitis, psoriasis before and after treatment with methotrexate, a potentially hepatotoxic drug) by immunohistochemical methods. Histologically normal liver biopsies from patients undergoing abdominal surgery served as normal controls. Hepatic parenchymal nerves were absent in cirrhotic nodules and were depleted in the fibrotic strands of alcoholic cirrhotic livers. In alcoholic hepatitis, where clinical and histological features associated with portal hypertension were absent, nerve fibers were increased around the portal vein branches. Similar increase was also noted in liver biopsies from patients with noncirrhotic portal hypertension. Increased numbers of nerve fibers around portal veins were demonstrated in psoriatics, particularly those treated with methotrexate. Immunohistochemical studies of extracellular matrix proteins revealed apparent inverse relationships between innervation and fibronectin deposition with direct relationships to laminin staining. The association of nerve network with portal hypertension and cellular inflammation was inconsistent.