Application value of immunoglobulin G4 detection in unexplained liver injuries

Abstract

Objective To investigate the expression level of immunoglobulin G (IgG)4 cells in patients previously diagnosed as unexplained liver injuries, and to analyze whether these patients could be diagnosed as immunoglobulin G4-related disease (IgG4-RD). The clinical characteristics of patients with IgG4 positive cells infiltration in liver tissues who did not met IgG4-RD diagnosis criteria were also analyzed. Methods From August 2010 to July 2016, 33 patients with unexplained liver injuries even after liver biopsy were enrolled. Immunostaining of IgG and IgG4 in liver tissue slices was performed. Whether the patients met the IgG4-RD diagnosis criteria was analyzed. Also, the relation between IgG4 positive cell infiltration in liver tissues and serum parameters (alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptadase (GGT), IgG), the classification of liver inflammation and stage of liver fibrosis were analyzed. Chi-square, Fisher exact probability method, t test and Wilcoxon rank and inspection were used for statistical analysis. Results Among 33 patients with unexplained liver injuries, average age of onset of the disease was (50.48±14.52) years old. Ten patients (30.3%) presented with different degree of IgG4 positive cells infiltration in liver. In one patient, the IgG4 positive cell number in liver tissue was over 10/high-powered field (HPF), IgG4+ /IgG+ ratio was over 40%, the serum IgG4 increased and low density nodules in the left hepatic lobe level, which met the diagnostic criteria of IgG4-RD. Serum parameters of liver function of this patient were as follows: ALT 948 U/L, AST 658 U/L, ALP 176 U/L, GGT 197 U/L, TBil 21.5 μmol/L, DBil 10.0 μmol/L. According to whether there were IgG4 positive cells infiltration in liver tissues, 33 patients were divided into IgG4 positive cells infiltration group (IgG4 positive group, 10 cases) and no IgG4 positive cells infiltration group (IgG4 negative group, 23 cases). The medium levels of ALT, AST, ALP and GGT in the IgG4 positive group and the IgG4 negative group were 26.0 U/L vs 31.0 U/L, 28.5 U/L vs 32.0 U/L, 114.0 U/L vs 77.0 U/L, 65.0 U/L vs 36.0 U/L, respectively and there were no statistically significant differences (Z=-0.098, -0.216, -0.862, -0.705; all P>0.05). The serum IgG level of the IgG4 positive group was higher than that of the IgG4 negative group (17.15 g/L vs 13.65 g/L), and the difference was statistically significant (Z=-1.776, P=0.035). Conclusions IgG4-RD may be the reason of liver injury. There are no significant differences in clinical charateristics, serum parameters and inflammation degree in liver tissue between patients with or without IgG4 positive cells infiltration. Key words: Unexplained liver injury; Immunoglobulin G4; Immunoglobulin G4-related disease