Association of baseline anti-Ro52 seropositivity with connective tissue disease development following interferon-α therapy in patients with chronic hepatitis B.

BACKGROUND: The aim of this study was to investigate whether baseline anti-Ro52 positivity was associated with the connective tissue disease (CTD) development in patients with chronic hepatitis B (CHB) receiving interferon-α (IFN-α) therapy. DESIGN: We conducted a retrospective cohort study of patients with CHB who initiated IFN-α therapy between January 2021 and December 2023. Associations between baseline anti-Ro52 positivity and CTD development were evaluated using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: A total of 1178 patients were included. Nine percent of CHB patients were positive for anti-Ro52 before IFN-α therapy and that 19.02% were positive after IFN-α therapy. There were 120 newly developed CTDs (120/1178, 10.19%) during IFN-α therapy, most of which were undifferentiated CTDs (UCTDs) (110/120, 91.67%). No statistically significant difference in CTD incidence was observed between the anti-Ro52 - and anti-Ro52 + groups (9.79% vs. 14.15%, P = 0.176). Multivariate Cox regression analyses revealed that female sex (HR = 1.53; 95% CI: 1.01-2.33; P = 0.045), IFN-α therapy duration ≥ 12 months (HR = 2.41; 95% CI: 1.62-3.59; P < 0.001), anti-Ro60 positivity (HR = 3.82; 95% CI: 1.82-8.03; P < 0.001), and Scl-70 positivity (HR = 5.65; 95% CI: 1.37-23.36; P = 0.017) were risk factors for CTD development in CHB patients after IFN-α therapy, whereas IFN-α therapy combined with NA therapy was associated with a decreased risk (HR = 0.56; 95% CI: 0.33-0.95; P = 0.031). CONCLUSION: Baseline anti-Ro52 positivity was not significantly associated with CTD development in patients with CHB receiving IFN-α therapy. Instead, CTD development appears to be associated with multiple clinical and serological characteristics, including female sex, prolonged IFN-α therapy, baseline anti-Ro60 positivity, and anti-Scl-70 positivity. Prospective studies with larger cohorts and longer follow-up are warranted to confirm these observations. Key Points • Anti-Ro52 positivity is common in CHB patients and significantly increased after IFN-α therapy. • Baseline anti-Ro52 positivity alone does not appear to be associated with subsequent CTD development in patients with CHB receiving IFN-α therapy. • Female sex, a duration of IFN-α therapy longer than 12 months, anti-Ro60 positivity, and anti-Scl70 positivity were associated with CTD development.