Project Details

Targeting Immune Pathways to Distinguish Autoimmune Hepatitis From Metabolic Dysfunction-Associated Steatotic Liver Disease

Silvia Nastasio, MD

Summary

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of pediatric liver disease, affecting approximately 10% of the pediatric population in the U.S and 38% of children with obesity. In contrast, pediatric autoimmune hepatitis (AIH) is a rare and progressive immune-mediated liver disease. Although these two conditions are clinically distinct entities requiring fundamentally different treatments, they share overlapping laboratory features and both can culminate in fibrosis, cirrhosis, and liver failure. The only definitive test that differentiates MASLD from AIH is a liver biopsy, which in AIH reveals characteristic infiltration by T cells and plasma cells. However, liver biopsies are invasive procedures that require general anesthesia and carry risks of bleeding and infection. Thus, we aim to improve the diagnostic precision for patients with AIH or MASLD by defining novel non-invasive biomarkers. GAP: This project addresses the lack of mechanistically informed blood biomarkers and the current reliance on invasive liver biopsy to distinguish AIH from MASLD. HYPOTHESIS: Our central hypothesis is that distinct immune signatures underlie autoimmune hepatitis and that characterization of these disease-specific immune pathways will enable the discovery of mechanistically informed blood biomarkers to differentiate AIH from MASLD. METHODS: This prospective translational study will leverage our existing pediatric liver disease biorepository, expanded to include 50 children with AIH, 100 with MASLD, and 50 healthy controls. Clinical data, plasma samples, and remnant liver biopsy tissue will undergo complementary immunologic and spatial tissue profiling to identify and validate disease-specific immune pathways. RESULTS: Pending. IMPACT: This study will provide new insight into the immune mechanisms underlying pediatric AIH while identifying non-invasive, mechanistically informed biomarkers that distinguish AIH from MASLD and reducing reliance on invasive liver biopsy to differentiate these two conditions.