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Association of Antiviral Therapy With Risk of Parkinson Disease in Patients With Chronic Hepatitis C Virus Infection

Educational Objective
To determine whether interferon-based antiviral therapy in patients with chronic hepatitis C virus infection is associated with incidence of Parkinson disease.
1 Credit CME
Key Points

Question  Is interferon-based antiviral therapy associated with Parkinson disease incidence in patients with chronic hepatitis C virus infection?

Findings  In this cohort study of 188 152 patients with hepatitis C virus infection, the group treated with antiviral therapy had lower incidence density and risk of developing PD compared with the untreated group.

Meaning  Results of treatment with interferon-based antiviral therapy appeared to support the hypothesis that hepatitis C virus may be a probable risk factor for Parkinson disease.


Importance  Epidemiologic evidence suggests that hepatitis C virus (HCV) could be a risk factor for Parkinson disease (PD), but treatment for HCV infection has never been considered in these studies; hence, the association between antiviral therapy and PD incidence has remained unclear. Understanding this association may help in developing strategies to reduce PD occurrence.

Objective  To identify the risk of PD development in patients with HCV infection receiving antiviral treatment and in patients not receiving this treatment.

Design, Setting, and Participants  This cohort study obtained claims data from the Taiwan National Health Insurance Research Database. Adult patients with a new HCV diagnosis with or without hepatitis per International Classification of Diseases, Ninth Revision, Clinical Modification codes and anti-PD medications from January 1, 2003, to December 31, 2013, were selected for inclusion. After excluding participants not eligible for analysis, the remaining patients (n = 188 152) were categorized into treated and untreated groups according to whether they received antiviral therapy. Propensity score matching was performed to balance the covariates across groups for comparison of main outcomes. This study was conducted from July 1, 2017, to December 31, 2017.

Main Outcomes and Measures  Development of PD was the main outcome. A Cox proportional hazards regression model was used to compare the risk of PD, and the hazard ratio (HR) was calculated at 1 year, 3 years, and 5 years after the index date and at the end of the cohort.

Results  A total of 188 152 patients were included in the analysis. An equal number (n = 39 936) and comparable characteristics of participants were retained in the treated group (with 17 970 female [45.0%] and a mean [SD] age of 52.8 [11.4] years) and untreated group (with 17 725 female [44.4%] and a mean [SD] age of 52.5 [12.9] years) after matching. The incidence density of PD was 1.00 (95% CI, 0.85-1.15) in the treated group and 1.39 (95% CI, 1.21-1.57) per 1000 person-years in the untreated group. The advantage of antiviral therapy reached statistical significance at the 5-year follow-up (HR, 0.75; 95% CI, 0.59-0.96), and this advantage continued to increase until the end of follow-up (HR, 0.71; 95% CI, 0.58-0.87).

Conclusions and Relevance  Evidence suggested that the PD incidence was lower in patients with chronic HCV infection who received interferon-based antiviral therapy; this finding may support the hypothesis that HCV could be a risk factor for PD.

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Article Information

Accepted for Publication: March 18, 2019.

Corresponding Authors: Ying-Zu Huang, MD, PhD (, and Rou-Shayn Chen, MD (, Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing St, Guishan District, Taoyuan, Taiwan 333.

Published Online: June 5, 2019. doi:10.1001/jamaneurol.2019.1368

Author Contributions: Drs W.-Y. Lin and M.-S. Lin contributed equally to the work. Drs Chen and Huang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: M.-S. Lin, Weng, Fong, Wu, Lu, Huang.

Acquisition, analysis, or interpretation of data: W.-Y. Lin, M.-S. Lin, Yeh, Y.-S. Lin, Chen.

Drafting of the manuscript: W.-Y. Lin, Yeh.

Critical revision of the manuscript for important intellectual content: M.-S. Lin, Weng, Y.-S. Lin, Fong, Wu, Lu, Chen, Huang.

Statistical analysis: W.-Y. Lin, M.-S. Lin, Y.-S. Lin.

Obtained funding: W.-Y. Lin.

Administrative, technical, or material support: W.-Y. Lin, M.-S. Lin, Yeh, Lu.

Supervision: Weng, Wu, Lu, Chen, Huang.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded by grant BMRPD45 from Chang Gung Medical Research Fund of Chang Gung Memorial Hospital, Linkou and by grant CMRPGME0011 from Chang Gung Memorial Hospital, Chiayi.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Meeting Presentation: This paper was presented as a poster at the 5th World Parkinson Congress; June 6, 2019; Kyoto, Japan.

Additional Contributions: We thank Alfred Hsing-Fen Lin, MS, and Zoe Ya-Jhu Syu, MPH, Raising Statistics Consultant Inc, for their statistical assistance. These individuals received compensation and declared no competing interest between the findings of this study and their company.

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