Roles of Fas/FasL and Complement Activation in Adult Patients With Chronic Active Epstein-Barr Virus Hepatitis

Background: Chronic active Epstein-Barr virus hepatitis (CAEBVH) in adult patients is a rare and highly lethal disease characterized by hepatitis and hepatomegaly.Aims: To investigate the clinicopathological features and pathogenic mechanisms in patients with CAEBVH.Methods:10 adult patients confirmed CAEBVH infection were collected. The clinicopathological characteristics were summarized and analyzed by clinical data. Flow cytometry to detect peripheral blood immune cell phenotypes, second-generation sequencing methods to explore pathogenic mechanisms, and immunohistochemical methods to verify pathogenic mechanisms.Results: The clinical features included splenomegaly, hepatomegaly, abnormal liver function, and CD8+T lymphopenia. HE also showed lymphocytic infiltration in liver tissue. EBER-ISH in lymphocytes of liver tissues were positive. Whole exon sequencing showed mutant genes were primarily enriched in 'T cell activation' and 'Complement and coagulation cascades'. The expression of CD8 in the CAEBVH group was higher than the controls in liver tissue (p<0.05). The same as the expression of Fas, FasL, Caspase-8, and TUNEL assay (p<0.05). Complement 1q (C1q) of liver sinusoidal endothelial cells (LSECs) and Glisson's capsule (GC), as well as Complement 3d (C3d) of LSECs, were a higher expression in CAEBV infection than controls (p<0.05).Conclusion: Fas/FasL and complement activation were involved in adult patients with chronic active Epstein-Barr virus hepatitis.