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, 54 (3), 940-8

Utility of Serum Immunoglobulin G4 in Distinguishing Immunoglobulin G4-associated Cholangitis From Cholangiocarcinoma


Utility of Serum Immunoglobulin G4 in Distinguishing Immunoglobulin G4-associated Cholangitis From Cholangiocarcinoma

Abdul M Oseini et al. Hepatology.


Elevated serum immunoglobulin G4 (sIgG4) is a feature of autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC); a >2-fold increase in sIgG4 is considered highly specific for these disorders. Many patients with IAC present with biliary strictures and obstructive jaundice, making cholangiocarcinoma (CCA) an important differential diagnosis. We determined the value of sIgG4 in distinguishing IAC from CCA. sIgG4 levels were measured in a test cohort of 126 CCA and 50 IAC patients. The results were confirmed in a validation cohort of 161 CCA and 47 IAC patients. Of the 126 CCA patients in the test cohort, 17 (13.5%) had elevated sIgG4 (>140 mg/dL) and four (3.2%) had a >2-fold (>280 mg/dL) increase. Primary sclerosing cholangitis (PSC) was present in 31/126 CCA patients, of whom seven (22.6%) had elevated sIgG4 and two (6.5%) had a >2-fold elevation. Of the 50 IAC patients, 39 (78.0%) had elevated sIgG4 and 25 (50.0%) had a >2-fold increase. The results in the validation cohort were consistent with those of the test cohort.

Conclusion: Although elevated sIgG4 levels are characteristic of IAC, some patients with CCA, particularly with PSC, have elevated sIgG4 levels, including a small percentage with a more than a 2-fold increase in sIgG4. Therefore, sIgG4 elevation alone does not exclude the diagnosis of CCA. Depending on the prevalence of the two diagnoses, the use of a 2-fold cutoff for sIgG4 may not reliably distinguish IAC from CCA. At a cutoff of 4 times the upper limit of normal, sIgG4 is 100% specific for IAC.

Conflict of interest statement

Conflicts of Interest: No conflicts of interest exist


Figure 1
Figure 1. Outline of the Study Groups
All CCA = All cases of Cholangiocarcinoma; PSC = Primary Sclerosing Cholangitis; CCA+PSC (CCA with concomitant PSC); CCA−PSC (CCA without PSC); IAC (IgG4-Associated Cholangitis).
Figure 2
Figure 2. Scatter plots of serum IgG4 in the different study groups in the test (Figure 2A) and validation cohort (Figure 2B)
Cut-offs of 1xULN (>140mg/dL) and 2xULN (>280mg/dL) are shown as dotted lines. The y-axis has a square root scale.
Figure 3
Figure 3. Receiver operating characteristic (ROC) curves of IgG4 for diagnosis of IAC versus All CCA patients in the test and validation cohorts
ROC curve of Sensitivity plotted against 1-Specificity of IgG4 in 50 IAC cases and All 126 CCA controls in the test cohort (A) and in 47 IAC and All 161 CCA controls in the validation cohort (B). The areas under the ROC curve are 0.87 and 0.80, respectively.
Figure 4
Figure 4
Survival curves of CCA patients with normal and elevated sIgG4 levels in the test (Figure 4A), validation (Figure 4B), and combined (Figure 4C) cohorts

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