BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system, characterized by pathogenic anti-Aquaporin-4 antibodies (AQP4-Ab). Given that infections can trigger autoimmune responses, we investigated the association between Hepatitis B virus (HBV) infection and NMOSD. MethodsHBV and hepatitis C virus serologies were analyzed in 105 NMOSD patients, 85 multiple sclerosis (MS) patients, and 1,661 healthy Taiwanese controls. Participants were classified into four HBV infection statuses (acute, chronic, resolved, and never infected), and further grouped by vaccination status. Logistic regression was used to estimate odds ratios (OR) for NMOSD development in individuals with chronic or resolved HBV infection. ResultsAmong those born before the Taiwan's universal vaccination program, 63.4 % of NMOSD patients had resolved HBV infection, compared to 30.6 % of MS patients and 16.4 % of controls. Resolved HBV infection was associated with a 2.3-fold increased risk for NMOSD development (95 % CI, 1.4–3.8), but not with MS risk. In the post-vaccination cohort, resolved HBV infection remained more frequent in NMOSD patients (8.7 %) than in MS (0 %) and controls (1.8 %). NMOSD patients with resolved HBV infection had later disease onset by 14.6 years and higher Expanded Disability Status Scale (EDSS) scores compared to those without HBV infection, even after adjusting for age and sex (3.5 ± 1.9 vs. 2.2 ± 1.8, p < 0.001). ConclusionPreceding HBV infection is prevalent among Taiwanese NMOSD patients and is associated with increased disease risk, older age at onset, and greater disability. Screening for HBV is essential for NMOSD patients, particularly in endemic regions.
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