Considerations for the Use of Serum IgG4, Total Bilirubin (TBIL)and the IgG4/TBIL Ratioindifferential Diagnosis Between IgG4-related Sclerosing Cholangitis and Cholangiocarcinoma

Abstract Background:Obstructive jaundice is the most frequent even theonly manifestation of both IgG4-related sclerosing cholangitis (IgG4-SC) and Cholangiocarcinoma(CCA). It was difficult to distinguish this two diseases, though the treatment strategies were quite different. Serum IgG4elevation was most frequently seen in IgG4-SC patients, yet the significantly elevated serum IgG4 in several CCA patients should not be neglected. Likewise, the serum level of IgG4 could be interfered by the serumlevel of TBIL.None of the previous research effort examined the differentiation potential of serumIgG4, CA19-9, TBIL and theIgG4/TBIL ratio for IgG4-SC and CCA. Methods: Atotalof202cases(131 cases of CCA and 71 cases of IgG4-SC) with pathology results were retrospectively registered. The data of serum IgG4,TBIL and the IgG4/TBIL ratio was captured. ROC-curve analysis was then applied to calculatedthe optimal cutoff values.Results: A significantly higher number of IgG4-SC patients experienced abdominal pain than CCA patients (P = 0.006).Elevationof the serum IgG4observedin IgG4-SCandCCAcasesshowed significant differences(P<0.0001). The optimal value of theIgG4 and the ratio was 1780 (95.3% sensitivity and 94.9% specificity) and 36.10 (96.9% sensitivity and 94.9% specificity)for differential diagnosis of IgG4-SC, respectively.For patients with elevation of serum IgG4 ranging from 650 to 3000 mg/L in 30.1% of all patients and 28.1% IAC patients, the serum levels of IgG4 and the ratio showed stronger differential diagnostic power (AUC=0.873 and AUC=0.968, respectively). The optimal value of the sIgG4 and the ratio was 1685 (with 88.9% sensitivity and 84.2% specificity) and 56.02 (94.4% sensitivity, 94.7% specificity). The combination of serum IgG4 and the IgG4/TBILpresentedhigher specificity(98.5%) andaccuracy(99.2%).Conclusion:The differences were significant in the serumlevel of IgG4, CA19-9 and the ratio. The IgG4/TBIL ratio has strongerdiscriminationefficiencythan the serum level of IgG4 or TBIL alonefor patients with elevation of serum IgG4 ranging from 650 to 3000 mg/L. The combination of the IgG4 and the IgG4/TBIL ratio could further enhance the specificity and accuracy for differentiatingIgG4-SCfrom CCA, especially in patients with serum IgG4 from 650 to 3000 mg/L.