Association between nucleos(t)ide analogue therapy for hepatitis B and Sjögren's syndrome: 15-year analysis of the national database of Taiwan.

Hepatitis B virus (HBV) infection has been proposed to play a role in the development of Sjogren's syndrome. However, to date, there are no reports on the risk of SS in HBV-infected patients following nucleos(t)ide analogue therapy. Due to Taiwan has higher prevalence of HBV infection and therapy was well recorded in the Taiwan's single-payer national health insurance database, we hypothesized that a long-term retrospective analysis of the risk of Sjogren's syndrome in HBV-infected patients following nucleotide therapy will increase our understanding of Sjogren's syndrome development following HBV infection. We identified 26,147 adults diagnosed with HBV infection between 1997 and 2012 in claims data. Finally, a total of 3268 HBV-infected patients who ever received nucleotide therapy (treated cohort) were frequency-matched on age and sex at 1:4 ratios to select a control group of 13,072 counterparts without therapy (untreated cohort). To identify Sjogren's syndrome risk, competing risk analysis adjusted for all covariates was performed. The risk was significantly lower in the treated cohort (15-year cumulative incidence, 2.4%; 95% confidence interval [CI], 1.4%-3.7%) than in the untreated cohort (7.1%; 95% CI, 2.5%-15.2%) (p = .015), and the adjusted HR was 0.6 (95% CI, 0.41-0.88; p = .009). Multivariable stratified analysis further verified the consistent associations between nucleoside therapy and risk reduction of Sjogren's syndrome across all strata. Our finding suggests that HBV infection treated with nucleotides is associated with lower risk of Sjogren's syndrome, implying a potential role of HBV infection in the development of Sjogren's syndrome.