13R-120) because this research was a retrospective observational study and did not use genetic screening or additional samples from patients. was female (80.0%), and the distribution was comparable to that of the classical-AIH patients. The IgG4-AIH patients exhibited significantly more severe phenotypes in portal inflammation, interface hepatitis, fibrosis, and rosette formation. All clinical laboratory data were comparable except for serum IgG4 levels, which were higher in IgG4-AIH patients (168.5 vs. 22.9 mg/dL, = 0.014). During a median follow-up period of 139 months, the relapse rate was significantly lower in the IgG4-AIH group PI4KIIIbeta-IN-9 than in the classical-AIH group (11.1 vs. 49.2%; = 0.048). Twelve (16.2%) and 6 (8.1%) classical-AIH patients underwent liver-related events and liver-related deaths, respectively. In contrast, none of the IgG4-AIH patients progressed to severe liver disease. Conclusions The IgG4-AIH patients had more severe inflammation and advanced fibrosis in the liver. However, their prognosis was not poor compared to that of classical-AIH patients. IgG4-AIH may have a phenotype unique from classical-AIH. values 0.05 were considered statistically significant. Results Characteristics of the Study Populace We enrolled 84 patients: 72 (85.7%) and 12 (14.3%) patients were diagnosed as definite and probable AIH according to the IAIHG score (Table ?(Table1).1). Of the 84 patients, 10 (11.9%) and 74 (88.1%) patients were categorized to IgG4- and classical-AIH, respectively (Fig. ?(Fig.1b).1b). The number of IgG4-positive plasma cells and the IgG4/IgG ratio were 5.4 4.5 (mean standard deviation [SD]) cells/HPF and 15.1 11.8%, respectively, in the IgG4-AIH group, whereas they were 0.3 0.6 cells/HPF and 2.0 4.8%, respectively, in the classical-AIH group. Notably, IgG4-positive plasma cells were not observed in 53 patients (63.1%). There were significant positive correlations between the quantity of IgG- and IgG4-positive plasma cells in the liver tissue (correlation coefficient = 0.352, = 0.001; Fig. ?Fig.2a)2a) and between the serum IgG4 levels and the number of IgG4-positive plasma cells in the liver tissue (correlation coefficient = 0.548, = 0.002; Fig. ?Fig.2b).2b). The best cutoff value (Youden index) for the number of IgG4-positive plasma cells using the ROC curve for serum IgG4 level 135 mg/dL was 2.7 cells/HPF with the area under the curve of 0.89, sensitivity of 80%, and specificity of 100%. As a result, we adopted 3 or more IgG4-positive plasma cells/HPF as part of the PI4KIIIbeta-IN-9 definition of IgG4-AIH. Open in a separate windows Fig. 2 a Correlations between the quantity of IgG-positive plasma cells and the number of IgG4-positive plasma cells in the liver tissue (Pearson’s rank correlation coefficient). b Correlations between the serum IgG4 levels and the number Rabbit Polyclonal to C/EBP-epsilon of IgG4-positive plasma cells in the liver tissue (Pearson’s rank correlation coefficient). Ig, immunoglobulin. Table 1 Clinical characteristics of patients at the time of diagnosis = 84)= 10)= 74)value(%)15 (20.3)0 (0)15 (20.3)0.123IAIHG score18 (11C22)18 (15C20)17 (11C22)0.442Definite, (%)72 (85.7)8 (80.0)64 (86.5)0.436Probable, (%)12 (14.3)2 (20.0)10 (13.5)ANA x80/160C640/1,280C2,56018/39/271/6/317/33/240.560ASMA positivity, (%)15/35 (42.9)2/5 (40.0)13/30 (43.3)0.893Albumin, g/dL3.8 (2.5C4.7)3.9 (3.2C4.4)3.8 (2.5C4.7)0.302AST, IU/L140 (14C1,581)201 (24C974)118 (14C1,581)0.317ALT, IU/L174 (9C2,757)182 (59C834)175 (9C2,757)0.857ALP, IU/L381 (106C2,215)514 (179C1,820)378 (106C2,215)0.243Total bilirubin, mg/dL0.8 (0.3C17.2)0.9 (0.4C3.3)0.8 (0.3C17.2)0.781Serum IgG, mg/dL2,343 (934C4,161)2,587 (1,824C4,090)2,332 (934C4,161)0.407Serum IgG4, mg/dL35.7 (3.7C281)a168.5 (139.4C281)b22.9 (3.7C198)c0.014Cirrhosis at diagnosis, (%)4 (4.8)1 (10.0)3 (4.1)0.12Start of treatment with PSL, (%)72 (85.7)9 (90.0)63 (85.1)0.564 Open in a separate window Data are expressed as median (range) or (%). AIH, autoimmune hepatitis; IAHG, International Autoimmune Hepatitis Group; ANA, antinuclear antibody; ASMA, anti-smooth muscle mass antibody; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; Ig, immunoglobulin; PI4KIIIbeta-IN-9 PSL, prednisolone. a= 30. b= 4. c= 26. Comparison between IgG4-AIH and Classical-AIH at PI4KIIIbeta-IN-9 Baseline The median age of the IgG4-AIH patients was 67 (range: 53C85) years, and the majority were female (80.0%). This distribution was similar to the classical-AIH patients (age: 62 [range: 20C82] years, female: 85.1%). Fifteen patients PI4KIIIbeta-IN-9 (20.3%) in the classical-AIH group had concurrent autoimmune diseases (5 with Sj?gren’s syndrome, 4 with systemic lupus erythematosus, 2 with autoimmune thyroiditis, etc.), whereas the IgG4-AIH patients did not have any concurrent autoimmune diseases (= 0.123). Clinical laboratory data including serum albumin, aspartate aminotransferase, ALT, alkaline phosphatase, total bilirubin, IgG, the positive rate of ASMA, and the ANA titer were not significantly different between the 2 groups. On the other hand, serum IgG4 levels were significantly higher in the IgG4-AIH (= 4) than the classical-AIH patients (= 26) (median: 168.5 [range: 139.4C281] mg/dL vs. median: 22.9 [range: 3.7C198] mg/dL, = 0.014). One IgG4-AIH and 3 classical-AIH patients experienced LC at AIH diagnosis (= 0.12). None of the IgG4-AIH patients revealed any abnormal findings in the pancreas and bile ducts suggestive of IgG4-related diseases (IgG4-RD) at the diagnosis and during the study period. In terms of liver histology, the IgG4-AIH patients revealed a significantly severer phenotype than the classical-AIH patients in portal inflammation (2.8 0.6 [mean SD] vs. 2.2 0.8, = 0.018), interface hepatitis (3.2 0.6 vs. 2.2 1.2, = 0.01), fibrosis (3.9 1.2 vs..