Background/Purpose: Systemic Juvenile Idiopathic Arthritis (SJIA) can present with or without Macrophage Activation Syndrome (MAS), a severe, potentially life-threatening complication. Liver tissue injury is commonly seen in SJIA patients and could be due to various reasons including underlying SJIA activity, MAS, drug hypersensitivity, and steatohepatitis among others. The objective of this study was to compare liver histopathology between SJIA patients with and without clinical MAS.

Methods: Liver tissue was obtained from two cohorts of SJIA patients: with clinical MAS (n=4) and without clinical MAS (n=6). H&E staining in addition to staining for CD3, CD4, CD8 (T-lymphocytes markers), CD163 (macrophage marker), CD79a (B lymphocyte marker) was performed. Histopathologic features including the density and composition of portal and sinusoidal infiltrate, interface necrosis, hepatocellular necrosis, hemophagocytosis, lymphocyte-mediated bile duct damage, cholestasis, and percentage and distribution of steatosis were examined by board-certified pediatric pathologists (LB and RS and JP).

Results: SJIA-MAS group was characterized by a more extensive portal and sinusoidal inflammatory CD3+ CD8+ T-cell and sinusoidal CD163+ macrophage infiltrate when compared to the SJIA-without MAS group. In particular, the SJIA-MAS group had a diffuse sinusoidal pattern of activated CD163+ macrophages in response to more extensive hepatocellular damage, including prominent centrilobular parenchymal collapse and multifocal hepatocellular necrosis with lymphocyte-mediate bile duct injury. In the SJIA without MAS group, CD163+ sinusoidal staining was present but showed a predominantly quiescent (inactive) pattern, highlighting the resident Kupffer cells with less hepatocellular injury.  Hepatocellular steatosis was present in 4/6 SJIA without MAS cases, involving less than 33% of the parenchyma, while none of the SJIA-MAS cases showed significant steatosis (< 1%).

Conclusion: Liver biopsies in SJIA patients with MAS demonstrate portal and sinusoidal cytotoxic T-lymphocytic injury and a sinusoidal infiltrate of activated macrophages correlating with more extensive hepatocellular damage compared to those SJIA patient without clinical MAS. These findings underscore the distinct hepatic pathology in SJIA patients with clinical MAS and highlight the importance of histopathological evaluation in the management of these patients. Future spatial transcriptomics work will explore if these two groups have a distinct genetic signature at the cellular sublocalization level in liver tissue biopsies.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/histopathological-features-of-liver-tissue-biopsies-in-sjia-patients-with-and-without-clinical-macrophage-activation-syndrome/