The CA19-9/IgG4 ratio distinguishes between cholangiocarcinoma and IgG4-related cholangitis among patients with high IgG4 levels

Both immunoglobulin G4 (IgG4)-related cholangitis (IRC) and cholangiocarcinoma (CCA) patients can have biliary strictures, and a serum IgG4 concentration ≥135 mg/dL leads to a diagnostic dilemma. We aimed to identify alternative serum markers to distinguish CCA from IRC. Patients with biliary stricture and a serum IgG4 concentration ≥135 mg/dL (n = 131) were enrolled in a tertiary care center (2008–2023). Of the 102 IRC patients (median age: 66 years), 91 (89.2%) were males; of the 29 CAA patients (mean age: 68 years), 21 (72.4%) were males. CCA patients presented lower serum IgG4 (median: 176 vs. 734 mg/dL, p < 0.001), higher carbohydrate antigen 19-9 (CA19-9) (391 vs. 46.2 U/mL, p < 0.001) and a higher neutrophil‒lymphocyte ratio (NLR) (4.8 vs. 2.8, p < 0.001) than IRC patients. The NLR (95% CIOR: 1.035–2.623), CA19-9 (1.001–1.023) and IgG4 (0.974–0.999) were independently associated with a diagnosis of CCA. In differentiating CCA from IRC, the areas under the receiver operating characteristic curve (AUROCs) of the NLR (cutoff >3.45), CA19-9 (cutoff >148 U/mL), IgG4 (cutoff ≤421 mg/dL) and the CA19-9/IgG4 ratio (cutoff >0.327) were 0.748, 0.857, 0.907 and 0.942, respectively. To predict CCA, CA19-9/IgG4 had a greater AUROC than CA19-9 ( p = 0.0003) and the NLR ( p = 0.001); IgG4 had a greater AUROC than the NLR ( p = 0.0107), and the performance of CA19-9/IgG4 was better than that of IgG4 (Z value = 1.2688). In addition to the serum NLR, CA19-9, and IgG4 levels, the CA19-9/IgG4 ratio (cutoff ≥0.327) is a feasible marker with good performance for identifying CCA in patients with serum IgG4 levels ≥135 mg/dL and biliary stricture.