Primary sclerosing cholangitis with moderately elevated serum-IgG4 - characterization and outcome of a distinct variant phenotype.

BACKGROUND AND AIMS Immunoglobulin G4-associated cholangitis (IAC) is characterized by distinctly elevated immunoglobulin G4 in serum (sIgG4) and responds well to corticosteroid therapy. Primary Sclerosing Cholangitis (PSC) is a progressive liver disease without causal treatment options usually not responding to immunosuppression. Increased serum levels of sIgG4 in patients with PSC, that do not meet criteria of IAC, have been reported in 10%-25%. Therefore, we aimed to characterize this subgroup of patients in a retrospective, multicenter study. METHODS sIgG4 values of 289 patients with PSC from three German university hospitals were analysed. Patients with elevated sIgG4 levels were identified and further characterized by clinical and biochemical parameters and by cholangiographic presentation. Clinical endpoints, death and liver transplantation were compared between groups. Parameters associated with outcome were identified with Cox regression analysis. RESULTS 14.5% of patients with PSC showed increased sIgG4 levels (PSC-IgG4), presented with significantly higher (P < .02) albumin, aspartate-aminotransferase, bilirubin and alkaline phosphatase and had a significant lower prevalence of a concomitant autoimmune hepatitis (P = .025). Cholangiogram obtained via ERC showed extrahepatic dominant strictures more often in the PSC-IgG4 subgroup (P = .047). The disease severity models Amsterdam-Oxford-Score (P = .018) and Mayo-Risk-Score (P = .025) predicted lower survival rates for the PSC-IgG4 subgroup. Transplant-free survival after first diagnosis of PSC was shorter in patients with elevated sIgG4 (11.6 vs 15.1 years, P = .001). CONCLUSION Patients with PSC and elevated sIgG4 should be considered as a distinct subgroup, characterized by different clinical and cholangiographical features and are associated with an inferior outcome.