IgG4-Associated Cholangitis in Patients Resected for Presumed Perihilar Cholangiocarcinoma: a 30-Year Tertiary Care Experience

Am J Gastroenterol. 2018 May;113(5):765-772. doi: 10.1038/s41395-018-0036-5. Epub 2018 Mar 16.


Background: Distinguishing perihilar cholangiocarcinoma (PHC) from benign forms of sclerosing cholangitis affecting the hilar bile ducts is challenging, since histological confirmation of PHC is difficult to obtain and accurate non-invasive diagnostic tests are not available. IgG4-associated cholangitis (IAC), an imitator of PHC, may present with clinical and radiographical signs of PHC. IAC can be accurately diagnosed with a novel qPCR test. The aim of this study was to investigate the incidence and long-term activity of IAC in patients resected for PHC in a single tertiary center over a period of 30 years.

Methods: All patients with benign disease who underwent surgery for presumed PHC in our institute between 1984 and 2015 were identified. Benign liver and bile duct specimens were re-evaluated by a pathologist and scored according to international consensus pathology criteria for IgG4-related disease (IgG4-RD). Patients with benign disease still alive were followed-up and a clinical diagnosis of IAC was made using a combination of the HISORt group C (response to steroids) criteria and elevated serum IgG4 levels and/or the novel IgG4/IgG RNA ratio. Also, recurrent symptomatic disease at any time after surgery requiring immunosuppression was assessed.

Results: Out of 323 patients who underwent surgery for presumed PHC, 50 patients (15%) had benign disease. In 42% (n = 21/50) of these patients a histological (n = 17) or clinical (n = 4) diagnosis of IAC was established. The remaining patients were diagnosed with unclassified sclerosing inflammation, cystadenoma, or sclerosing hemangioma. Nine out of 12 IAC patients who were followed-up showed episodes of recurrent disease requiring immunosuppressive treatment.

Conclusions: Liver and bile duct resections for PHC during three decades disclosed in 15% benign biliary disorders mimicking PHC of which 42% were definitely diagnosed as IAC. IgG4-RD remains active in the majority of patients with IAC years after surgery. Novel diagnostic tests for IAC might reduce misdiagnosis, unnecessary surgery, and life-threatening complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / surgery
  • Bile Ducts / pathology
  • Bile Ducts / surgery
  • Cholangitis, Sclerosing / diagnosis*
  • Cholangitis, Sclerosing / epidemiology
  • Cholangitis, Sclerosing / immunology
  • Cholangitis, Sclerosing / therapy
  • Diagnosis, Differential
  • Diagnostic Errors / statistics & numerical data
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / immunology
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Klatskin Tumor / diagnosis*
  • Klatskin Tumor / mortality
  • Klatskin Tumor / pathology
  • Klatskin Tumor / surgery
  • Liver / pathology
  • Liver / surgery
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Recurrence
  • Retrospective Studies
  • Survival Rate
  • Tertiary Healthcare / statistics & numerical data*


  • Immunoglobulin G
  • Immunosuppressive Agents