Hepatic Manifestations in Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome

Objective Systemic juvenile idiopathic arthritis (SJIA) is a chronic inflammatory disease characterized by systemic features and arthritis. Macrophage activation syndrome (MAS) is a severe complication of SJIA often involving the liver. MAS confined predominantly to the liver, causing severe hepatitis, has been increasingly recognized. When liver MAS is the primary manifestation, significant hepatic injury can occur, requiring differentiation from other forms of SJIA-related liver involvement, which may warrant distinct treatment approaches. This study examined liver pathology in SJIA-MAS patients and explored potential mechanisms. Methods This retrospective case series analyzed data from four SJIA-MAS patients who presented with liver dysfunction and underwent core liver biopsies at Cincinnati Children's Hospital Medical Center (2019–2024). Results Four patients (age range 4 –15 years) had elevated transaminases, with one meeting MAS criteria and three diagnosed with subclinical MAS. Liver biopsies showed portal and sinusoidal inflammatory infiltrates of CD3+ CD8+ T cells and CD163+ macrophages, with extensive hepatocellular damage, including centrilobular parenchymal collapse, multifocal necrosis, and lymphocyte-mediated bile duct injury. One case revealed features of veno-occlusive disease (VOD), a novel finding. Elevated serum CXCL9 and rapid response to emapalumab (anti-IFNγ) in all patients suggested IFNγ-driven liver pathology. Conclusion This study underscores the critical roles of CD8+ T cells, macrophages, and IFNγ in SJIA-MAS hepatitis. Future research should explore whether serum biomarkers of IFNγ activity can differentiate SJIA-MAS from other liver pathologies, such as drug-induced liver injury (methotrexate or anakinra-induced) and hepatic steatosis, to guide tailored therapies.