PEDIATRIC AND ADULT METABOLIC-ASSOCIATED FATTY LIVER DISEASE (MAFLD): HEPATIC LYMPHOCYTES INVOLVED IN PATHOGENESIS

CAIROLI VICTORIA; DE MATTEO E; RÍOS D; LEZAMA, C.; GALOPPO, M.; CASCIATO P; MULLEN E; GIADANS C; BERTOT G; MARIA VICTORIA PRECIADO; VALVA P

Congreso; LXV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FISIOLOGÍA (SAFIS); 2020

Lipid accumulation, cellular damage and inflammation are involved in MAFLD pathogenesis. Liver inflammation is critical in disease progression, but the cellular infiltrate composition and the role of each lymphocyte population are still up for debate. Our aim was to characterize the inflammatory infiltrate present in the liver microenvironment both in children and adult MAFLD patients and to evaluate it according to damage severity. Twenty-six MAFLD pediatric patients [median age: 11.5 years (range 4-17)] and 35 adult patients [median age: 49 years (range 28-72)] were enrolled. Histological parameters as well as localization and frequency of Cytotoxic T Lymphocytes (CD8+), T helper Lymphocytes (CD4+), Regulatory T lymphocytes (Treg, Foxp3+) and Th17 (IL-17A+) were evaluated on formalin-fixed paraffin-embedded liver biopsies by staining and immunohistochemistry, respectively. In portal/periportal (P/P) tracts, there was a similar proportion of CD8+ and CD4+ lymphocytes, while CD8+ lymphocytes predominated in the intralobular area. IL-17A+ lymphocytes seemed to be nearly exclusive of P/P area. Age-groups comparison demonstrated higher P/P Foxp3+ (p=0.006, M-W test) and intralobular CD8+, CD4+ and Foxp3+ lymphocyte counts (p=0.025, p=0.0004 and p=0.013, respectively, M-W test), but lower P/P IL-17A+/Foxp3+ cell ratio (p=0.041 M-W test) in adults. Severe inflammation was associated with higher intralobular Foxp3+ lymphocytes (p=0.026 M-W test) in children, and lower P/P Foxp3+ and higher IL-17A+ lymphocytes in adults. All cases with fibrosis ≥2 displayed P/P low Foxp3+ and high IL-17A+ lymphocyte counts. Pediatric cases with worse steatosis showed high P/P CD4+ (p=0.023, t test) and intralobular CD8+ (p=0.027M-W test) and CD4+ cells (p=0.012M-W test). In MAFLD cases, the lymphocyte liver infiltrate composition differs between children and adults. Treg and Th17 balance seems to condition damage progression, denoting their important role in the pathogenesis.