Kupffer Cell Hyaline Globules in Children With Autoimmune Hepatitis

Abstract

Background: Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for being a typical feature of autoimmune hepatitis (AIH). This study aimed to determine how useful Kupffer cell hyaline globules (KCHGs) are in diagnosing AIH vs. other causes of pediatric chronic liver diseases (PCLDs). Materials and methods: This retrospective study recruited 124 children; 58 with AIH, 50 with chronic hepatitis C virus (HCV) infection, and 16 with Wilson's disease (WD). Two pathologists retrieved paraffin blocks of liver biopsies and prepared new cut sections for Periodic acid-Schiff-Diastase (PAS-D) stain. They independently examined liver biopsies before starting treatment. Two pediatricians reviewed medical records for demographic, clinical, laboratory, and serological findings. Results: Females represented 48.6% of the studied children with a median age of 5.8 (4.9) years. Pathologists identified KCHGs in 67.24%, 12.5%, and 6.0% of AIH, WD, and HCV affected children respectively, P < 0.001. A significantly higher proportion of seropositive than seronegative AIH patients had KCHGs (77.5% vs. 50.0%), P < 0.05. In multivariate analysis, KCHGs and prolonged prothrombin time were the only significant predictors that differentiate between AIH and the other studied PCLDs. The odds ratio of having AIH increased 68 times if KCHGs were seen. Among children with AIH, the presence of KCHGs was associated with higher median levels of direct bilirubin 2.2 (1.3) vs. 1.2 (2.2), and immunoglobulin G 3.2 (1.9) vs. 2.0 (1.7), P < 0.05, but not to histopathological findings or hepatic fibrosis and activity. Conclusions: KCHGs are key indicators that can differentiate between AIH and other PCLDs, and between seropositive and seronegative AIH.

Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity

“…The presence of hyaline globules in Kupffer cells has been suggested to serve as a diagnostic clue for AIH, and a modification of the 2008 IAIHG histology component has been proposed by Gurung et al, which requires the presence of Kupffer cell hyaline globules in addition to a prominent plasmacytic infiltration to qualify as a “typical” AIH [ 23 ]. However, this needs further validation; a few other studies demonstrated that this feature was not correlated with serum IgG levels, autoantibody status or histological activity/fibrosis, and moreover, its identification requires additional stains such as periodic acid-Schiff post-diastase (D-PAS) stain and CD68 [ 24 , 25 ]. Another interesting finding which requires further validation is the higher number of apoptotic lymphocytes in portal tractsin AIH compared to other liver diseases [ 26 ].…”

“…23 However, this needs further validation; a few other studies demonstrated that this feature was not correlated with serum IgG levels, autoantibody status or histological activity/fibrosis, and moreover, its identification requires additional stains such as periodic acid-Schiff post-diastase (D-PAS) stain and CD68. 24,25 Another interesting finding which requires further validation is the higher number of apoptotic lymphocytes in portal tracts in AIH compared to other liver diseases. 26 The limitations of this study are as follows.…”

Autoimmune Hepatitis in Children: A Single Center Experience: Descriptive Research

“…Bir çalışmada, karaciğer Kupffer hücrelerinde hiyalin globulin görülmesinin OİH'li hastaları diğer pediatrik kronik karaciğer hastalıklarından ve seropozitif OİH'yi seronegatiflerden ayırmada temel gösterge olabileceği belirtilmiştir. 21 Otoantikorlar dışında da tanıda kullanılabilecek patoloji bulgularının değerli olduğu söylenebilir.…”

Resident macrophages of the lung and liver: The guardians of our tissues

“…Immune cell driven inflammation is a central mechanism in the development and progression of AIH, and targeting this inflammation with immunosuppressive therapies is an effective treatment. Among the few reports discussing the role of KCs in AIH, most focused on the finding of hyaline droplets in the cytoplasm of these cells ( 167 , 168 ). In adults this histological feature was shared between samples with AIH and primary biliary cholangitis (PBC).…”