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

Abstract

\n 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.