There have been many reports about the severity of hepatic
necrosis caused by
fulminant hepatitis; however, the relation between proliferated bile ductules and
osteopontin (OPN) expression in inflamed areas in each of the clinical forms of
fulminant hepatitis has not been described. To analyze the mechanism in the onset of
fulminant hepatitis, we classified not only 16 autopsy cases of
fulminant hepatitis into two clinical forms--acute and subacute--but also 3 autopsy cases of late-onset
hepatic failure (LOHF) associated with
fulminant hepatitis, and examined liver specimens by light microscopy and immunohistochemistry and also serum
transaminase levels. Histopathologic study revealed that some of the proliferated bile ductules were associated directly with deteriorating hepatocytes and that bile plugs were present in the proliferated bile ductules. The value of the proliferative cell
nuclear antigen labeling index (
PCNA-L I) for proliferated bile ductules was very high during the acute form of
fulminant hepatitis. Immunohistochemical analysis revealed that OPN expression was higher in the proliferated bile ductules of acute-form
fulminant hepatitis than in cirrhotic and normal liver bile ducts.
Transaminase levels in acute-form
fulminant hepatitis were significantly elevated in comparison with levels in the other forms of the disease. Comparison of acute form
fulminant hepatitis with the subacute form and LOHF showed OPN expression in proliferated bile ductules and serum
aspartate aminotransferase (ALT)max to be decreased in the subacute form of
fulminant hepatitis. OPN expression is an important marker of the degree of liver
inflammation, and its regulation mechanism is very important to understanding the pathophysiology of
fulminant hepatitis.