Kupffer Cell Hyaline Globules in Children With Autoimmune Hepatitis

Mohammed A Khedr; Nermin M Adawy; Tahany A Salim; Menan E Salem; Ramy M Ghazy; Ahmed S Elharoun; Mervat M Sultan; Nermine A Ehsan

doi:10.1016/j.jceh.2021.04.013

Kupffer Cell Hyaline Globules in Children With Autoimmune Hepatitis

J Clin Exp Hepatol. 2022 Jan-Feb;12(1):20-28. doi: 10.1016/j.jceh.2021.04.013. Epub 2021 May 4.

Authors

Mohammed A Khedr¹, Nermin M Adawy¹, Tahany A Salim¹, Menan E Salem¹, Ramy M Ghazy², Ahmed S Elharoun³, Mervat M Sultan⁴, Nermine A Ehsan⁴

Affiliations

¹ Department of Pediatric Hepatology, Gastroenterology, and Nutrition, National Liver Institute, Menoufia University, Egypt.
² Tropical Health Department, High Institute of Public Health, Alexandria University, Egypt.
³ Microbiology and Immunology Department, Faculty of Medicine, Menoufia University, Egypt.
⁴ Department of Pathology, National Liver Institute, Menoufia University, Egypt.

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.

Keywords: AIH, Autoimmune hepatitis; ALP, Alkaline phosphatase; ALT, Alanine aminotransferase; AMA, Antimitochondrial antibody; ANA, Antinuclear antibody; AST, Aspartate aminotransferase; GGT, Gamma-glutamyl transpeptidase; H&E, Hematoxylin and eosin; HCV, Hepatitis C virus; IAIHG, International Autoimmune Hepatitis Group; KCHGs, Kupffer cell hyaline globules; KCs, Kupffer cells; Kupffer cells; LKMA, Liver-kidney microsome 1 antibody; PAS, Periodic Acid Schiff; PAS-D, Periodic acid–Schiff–Diastase; PCLD, Pediatric chronic liver disease; SMA, Smooth muscle antibody; WBCs, White blood cell count; WD, Wilson’s disease; Wilson’s disease; antiLC1, Antiliver cytosol type 1 antibody; autoimmune hepatitis; hepatitis C virus infection; hyaline globules; liver histopathology.