The long-term outcomes of patients with immunoglobulin G4-related sclerosing cholangitis: the Mayo Clinic experience

Abstract

Background The long-term outcomes of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are not well known. Methods The outcomes of patients with IgG4-SC at Mayo Clinic (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) were compared to an age-and gendermatched (1:1 ratio) group of patients with primary sclerosing cholangitis (PSC). Results We identified 89 patients with IgG4-SC; median age at diagnosis was 67 years, 81% were males, and the median follow-up was 5.7 years. Seventy-eight patients received prednisone for induction of remission, and 53 received at least one other immunosuppressive agent for maintenance of remission. Of the IgG4-SC group, 10 died (median time from diagnosis until death was 6.5 years): 2 due to cirrhosis, 3 due to cholangiocarcinoma (CCA), and 5 due to non-hepatobiliary causes. Eleven patients in the PSC group underwent liver transplantation, while none did in the IgG4-SC group. The incidence of a hepatobiliary adverse event (cirrhosis or CCA) was 3.4 times greater in the PSC compared to the IgG4-SC group (events per 1000 person-years: 52.6; 95% CI 38-73; vs. 15.6; 95% CI 7-32). The probability of development of a hepatobiliary adverse event within 10 years was 11% in the IgG4-SC compared to 45% in the PSC group (P = 0.0001). The overall survival tended to be higher in the IgG4-SC compared to the PSC group (10-year: 79% vs. 68%, respectively; P = 0.11). Conclusions In a cohort of IgG4-SC patients, 88% of whom were treated with immunosuppressive drugs, the risk of cirrhosis and CCA was significantly lower compared to an age-and gender-matched group with PSC.

IgG4‐related sclerosing cholangitis may be a risk factor for cancer

“…This result agrees with the previous study of AIP by Shiokawa et al 4 In particular, a previous studies have reported the diagnosis of bile duct cancer concurrently with the diagnosis of IgG4‐SC 5,16 . Cases of bile duct cancer diagnosed 4 months and 1.5 years after IgG4‐SC diagnosis reported 8,16 . In the present study, three cases were diagnosed with bile duct cancer.…”

“…Of the 121 IgG4-SC patients, 108 (89.3%) had AIP. In previous reports, 87%-89% of IgG4-SC cases coexisted with AIP, 8,16 similar to the present study. Although there may be a possibility of confounding factors, the SIR was higher in IgG4-SC without AIP was higher than IgG4-SC with AIP in the present study.…”

“…5,16 Cases of bile duct cancer diagnosed 4 months and 1.5 years after IgG4-SC diagnosis reported. 8,16 In the present study, three cases were diagnosed with bile duct cancer. There was one case diagnosed simultaneously, and the other was diagnosed with bile duct cancer one year after the diagnosis of IgG4-SC.…”

“…Additionally, in the pancreaticobiliary regions of AIP patients, KRAS mutation occurs frequently, 7 and AIP may be a factor for pancreaticobiliary cancer. Although the association between IgG4‐SC and bile duct cancer has been reported sporadically, 8 there are no reports of many cases regarding the details of the risk of cancer in IgG4‐SC. The relationship and details of IgG4‐SC with any type of cancer remains unclear.…”

Differentiating Primary Sclerosing Cholangitis from Similar Diseases of Autoimmune Origin

“…In the long term, PSC patients are at a significantly greater risk of cirrhosis and cholangiocarcinoma than are patients with IgG4-related SC [11].…”