High Prevalence of IgG4 Positive Immunohistochemical Cholangitis in Liver Explants from Patients with PSC.
Sammy Ali, Gideon M Hirschfield, Christopher Meaney, Paul D Greig, George Therapondos, Sandra E Fischer. University of Toronto, ON, Canada
Background: IgG4 associated cholangitis/pancreatitis is a highly steroid responsive inflammatory disease. As many as 10-15% of patients with primary sclerosing cholangitis (PSC) are reported to have elevated serum IgG4 levels, and this subpopulation may have a different natural history. IgG4 deposition histologically has been reported in explants from patients with PSC. The aim of the study is to confirm the prevalence of histological IgG4 associated cholangitis in patients undergoing liver transplantation for PSC.
Design: IgG4 immunohistochemistry was performed on liver explants from patients with PSC (n=123) and unrelated cholestatic and viral liver disease (n=50), using representative sections from the hilum. Positive IgG4 staining was defined either as ³10 positive IgG4 cells per high power field (HPF) or as no staining (<5 cells/HPF), mild staining (5-10 cells/HPF), moderate staining (11-29 cells/HPF) and marked staining (³30 cells/HPF). Immunochemical staining was compared to baseline lymphoplasmacytic inflammation. Clinical correlations with pre- and post-transplant variables were performed.
Results: Of the 50 control liver sections (PBC, n=19; HCV, n=19; HBV, n=8; AIH, n=6) none had marked staining and mild-moderate staining was seen in only one AIH explant, one PBC explant, and three HCV explants. In contrast of the 123 explants from patients with PSC studied, 59 (48.0%) had positive IgG4 immunohistochemical staining in hilar tissue (³10 cells per HPF). Forty two (34.1%) were classified as no IgG4 staining, 22 (17.9%) had mild staining, 28 (22.8%) moderate staining, and 31 (25.2%) had marked staining. Tissue IgG4 positivity was strongly correlated with moderate to marked periductal (hilar) lymphoplasmacytic inflammation (P<0.001) i.e. the inflammation surrounding the large hilar ducts which extends into adjacent tissue. Positive IgG4 staining was more likely in men (P=0.04), and in those with a history of pancreatitis (P=0.03). Other clinical parameters were unrelated to IgG4 staining, in particular age at diagnosis, presence of IBD and presence of recurrent disease.
Conclusions: A large number of patients undergoing transplantation for PSC have marked histological IgG4 plasmacytic cholangitis. Further characterization of the significance of this histological observation is required, as it raises the question of whether steroids may have a role in a sub-population of patients with PSC.
Category: Liver & Pancreas
Tuesday, March 1, 2011 2:00 PM
Platform Session: Section C, Tuesday Afternoon