Title Application and validation of a new histologic staging and grading systemfor primary biliary cirrhosis

Background:We proposed a new grading and staging system for primary biliary cirrhosis (PBC), which takes into account the degree of both chronic cholangitis activity (CA) and hepatitis activity (HA) for grading of disease activity and those of fibrosis, bile duct loss, and chronic cholestasis for staging. In this study, we validated our new system. Methods:Using liver biopsy specimens from 166 cases of PBC, chronic cholangitis with mild periductal lymphoplasmacytic infiltration including chronic nonsuppurative destructive cholangitis and combined activity of interface hepatitis and lobular hepatitis were categorized into four grades according to its degree and distribution (CA0-3 and HA0-3, respectively). For staging, because Orcein staining was not available in this study, two criteria (fibrosis and bile duct loss) were independently scored 0-3 according to their degrees and a final stage score was created from the sum. Results:Although there was a relatively uniform distribution among CA0/1/2/3, the cases of HA0/1/2/3 were distributed as 21%, 64%, 13%, and 3%, respectively, with a prominence of cases categorized with none and mild hepatic activity. The distribution of stages 1-4 with our system was considerably different from that with classical system, and importantly showed a correlation with patient's outcome. Conclusions:Our system revealed that the activities of chronic cholangitis and hepatitis did not correlate with each other in degree, and that our staging system properly reflected the outcome of the PBC patients. The present study could validate the effectiveness of this new systems for characterizing the pathological condition of PBC.