Peptidyl Arginine Deiminase: A Novel Immunohistochemical Marker for Liver Fibrosis in Patients with Chronic Hepatitis

Peptidylarginine deiminase (PAD) is an enzyme known to be involved in the pathogenesis of rheumatoid arthritis (RA). Since many of the molecular events present in the joints in RA also take place in the injured liver, we postulated in this study that PAD may be involved in liver fibrosis. The objectives of this study therefore were to find out if PAD could be demonstrated immunohistochemically in liver biopsies of patients with chronic hepatitis and if it is associated with METAVIR activity and fibrosis scores. Liver biopsies were obtained from 100 patients with chronic liver diseases between September 2006 and 2007. The biopsies were scored by two histopathologists according to the METAVIR activity and fibrosis scores after histological preparation. Immunohistochemistry for PAD was performed on the biopsies using a monoclonal antibody against PAD. PAD could not be demonstrated in normal liver biopsies but was found in the hepatocytes of patients with chronic hepatitis. PAD labeling could distinguish patients with no fibrosis from either F1 or F2 or F3 or F4 fibrosis. Similarly, PAD labeling could separate patients with no inflammatory activity from those with mild or moderate or severe activity. We concluded that PAD could be demonstrated immunohistochemically in liver biopsies of patients with chronic hepatitis and that its immunodetection was significantly associated with Metavir activity and fibrosis scores.