Association of nucleos(t)ide analogue therapy with Parkinson disease in chronic hepatitis B patients

Prolonged therapy using nucleos(t)ide analogs (NUC) is inevitable in patients with chronic hepatitis B (CHB) infection, but its long-term impact on Parkinson's disease (PD) risk remains unclear. This study evaluated the association between NUC therapy and PD incidence in a nationwide CHB cohort. The study population comprised the National Health Insurance Service claims database from January 1, 2013, to December 31, 2013, only included treatment naïve CHB patients and those without previously diagnosed with PD. Participants were followed until PD diagnosis or study completion. The primary outcome was PD incidence, comparing patients who initiated NUC therapy at cohort entry with those who did not. Over the 7.9-year study period, the incidence rate of PD in NUC-treated patients was 1.48 per 1000 persons, compared to 1.95 per 1000 persons in the untreated group. In an adjusted competing risk model, the 3-year follow-up showed a statistically significant reduction in risk (hazard ratio [HR]: 0.61; 95% confidence interval [CI] 0.39-0.97). In the propensity score-matched cohort of 18,365 pairs, the cumulative incidence during 2-4 years of follow-up was significantly lower in the NUC-treated group compared to the untreated group. However, no statistically significant difference in cumulative PD incidence was observed between the groups at the early or late stages of the follow-up period. NUC therapy initially reduced PD incidence, but this protective effect diminished over time, indicating a time-varying effect. Regular PD screening may be needed for long-term NUC users.