| ObjectiveIgG4-related disease(IgG4-RD)is a newly discovered immunological disease involving multiple organs,but the association with liver injury remain elusiveis.The etiological diagnosis of liver injury is still a hard problem.We have found that some liver injury patients with increased serum IgG4,the characteristics between serum IgG4 and liver injury need to be elucidated.In this study,we first collected liver tissues from patients with unexplained liver injury and immunohistochemically stained to clarify the association between IgG4-RD and liver injury.In addition,the clinical information of patients with increased serum IgG4 in Tianjin Medical University Medical Examination Center was collected,to identify the cause of liver injury with increased serum IgG4,the proportion of patients with liver injury was counted and the diagnosis of liver injury was analyzed.Finally,we analyzed characteristics in Th1 and Th2 cytokine profiles in liver injury patients with increased serum IgG4.MethodFirst part:The Diagnosis of IgG4-Related Liver DiseaseFrom August 2010 to July 2016,33 patients diagnosed as unexplained liver injury were enrolled.Immunostaining of IgG and IgG4 in liver tissue slices was performed,inflammation grade G and fibrosis stage S were determined,we want to analyze whether these patients could be reclassified as IgG4-RD.At the same time,serological indexes(alanine aminatransferase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),IgG,IgG4)of these patients were collected.Second part:The Diagnosis of the Liver Injury Patients with Increased Serum IgG4Patients with increased serum IgG4 were selected in Tianjin Medical University General Hospital between May 2012 and June 2017.Eighty-three patient cases were collected,including name,age,sex,past history,clinical presentation,complications,laboratory tests,imaging studies,diagnosis and treatment.By summarizing the proportion of patients with liver injury,we aim to analyze the diagnosis of liver injury and the sensitivity to glucocorticoid therapy in patients.Third part:The Th1/Th2 Cytokines of Paitents with Increased Serum IgG4Collected 16 cases of liver injury,8 cases of IgG4-RD,1 case of eosinophilic gastroenteritis and 1 case of unexplained liver injury from December 2016 to August2017 at the General Hospital of Tianjin Medical University.Milliplex multi-factor detection technique was used to detect cytokines in Th1/Th2 cells.ResultFirst part:IgG4-Related Liver Disease1.Among 33 patients,two patients were stained to reveal more than 10 IgG4~+cells per high-powered field(IgG4~+/HPF)in the liver.When reviewing of the laboratory datas and CT,they were suggested that an diagnosis of IgG4-related disease might be the reason for liver injury.2.The patients were divided into two groups:10 patients with IgG4~+plasma cells infiltration in liver and 23 patients without IgG4~+plasma cells infiltration in liver.There was no significant difference in serum levels of ALT,AST,ALP and GGT between patients with or without IgG4~+plasma cells in liver(all p>0.05).IgG serum level of patients with IgG4~+plasma cells infiltration in liver was higher compared to the patients without IgG4~+plasma cells infiltration in liver(p<0.05).Second part:The Diagnosis of the Liver Injury Patients with Increased Serum IgG41.83 patients mainly included IgG4-RD(37.3%),autoimmune liver disease(AILD)(13.2%),malignant tumor(12.0%),connective tissue disease(7.2%)and viral hepatitis(3.6%).2.Of the 83 patients,64 patients were liver injury,accounting for 72.3%.IgG4-RD patients with liver injury accounted for 34.4%(22/64),AILD 17.2%(11/64),malignant diseases 9.3%(6/64)and so on.3.There was no significant difference in serum IgG4 levels between patients with different etiologies of liver injury.4.Of the 22 IgG4-RD patients with liver injury,15 treated with glucocorticoid.After the glucocorticoid therapy,ALKP and DBIL improved significantly(p<0.05).Third part:The Th1/Th2 Cytokines of Patients with Increased Serum IgG41.Serum levels of IL-4 and IL-5 in liver injury patients with increased serum IgG4were significantly higher than those in healthy controls(p<0.05).2.The levels of IL-4,IL-5,IL-10,IL-13 and IL-21 in AIH patients with increased IgG4 were significantly higher than those in healthy controls(p<0.05).3.The levels of IL-4,IL-13 and IL-21 in AIH patients with increased IgG4 were significantly higher than those in IgG4-RD patients(p<0.05).4.The levels of IL-5 and IL-13 in AIH patients with increased IgG4 were significantly higher than those in AIH patients(p<0.05).Conclusion1.In this study,we found 2 cases of patients with unexplained liver injury who had been diagnosed with IgG4~+plasma cells after immunohistochemical staining,combined with serum IgG4 and imaging,they can be re-diagnosed as IgG4-related liver disease.It was suggested that IgG4-RD is a cause of the liver injury.2.There was no significant difference in the clinical characteristics,liver function index,grade and stage of liver inflammation in patients with or without IgG4~+plasma cells infiltration.3.The etiology of liver injury patients with increased serum IgG4 include IgG4-RD,AILD,malignant diseases and so on.4.Serum IL-4 and IL-5 levels in liver injury patients with elevated serum IgG4were significantly higher than those in healthy controls. |
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