Coexistence of VEXAS Syndrome and Chronic Hepatitis B Virus Infection: a Case Report and Literature Review.

Abstract

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently identified late-onset, X-linked autoinflammatory disorder caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene, which impair ubiquitination and protein degradation pathways. VEXAS is characterized by multisystem involvement, overlapping clinical features with other inflammatory conditions and high mortality. Despite growing attention, our understanding of its pathophysiology, immune dysregulation, and optimal treatments remains limited. This report aims to explore the molecular pathogenesis, diagnostic criteria, and therapeutic approaches for VEXAS syndrome in the context of chronic hepatitis B virus (HBV) infection. A 68-year-old Chinese male patient presented with persistent fever, fatigue, arthritis, weight loss, and hematologic abnormalities (severe macrocytic anemia and thrombocytopenia). Genetic testing revealed a somatic UBA1 mutation (p.Met41Val, c.121A > G, 67.84%) in myeloid cells, confirming VEXAS syndrome. The patient also had chronic HBV infection with active viral replication. Treatment included antiviral therapy (entecavir) for HBV and a combination of corticosteroids and immunosuppressants for VEXAS syndrome. After a follow-up of 6 months, significant improvements were observed in clinical symptoms, hematologic parameters, and inflammatory markers. This case highlights the interplay between chronic HBV infection and VEXAS syndrome-mediated immune dysregulation. Integrated antiviral and immunosuppressive strategies are essential to manage VEXAS syndrome with chronic hepatitis B virus comorbidity. Future studies should focus on targeted therapies, such as JAK-STAT inhibitors and IL-6 blockade, to improve outcomes in patients with chronic viral infections and VEXAS syndrome.