Abstract
Background: Whether infection with the hepatitis C virus (HCV) causes schizophrenia — and whether the associated risk reverses after anti-HCV therapy — is unknown; we aimed to investigate these topics.
Methods: We conducted a nationwide, population-based cohort study using the Taiwan National Health Insurance Research Database (TNHIRD). A diagnosis of schizophrenia was based on criteria from the International Classification of Diseases, 9th revision (295.xx).
Results: From 2003 to 2012, from a total population of 19 298 735, we enrolled 3 propensity-score-matched cohorts (1:2:2): HCV-treated (8931 HCV-infected patients who had received interferon-based therapy for ≥ 6 months); HCV-untreated (17 862); and HCV-uninfected (17 862) from the TNHIRD. Of the total sample (44 655), 82.81% (36 980) were 40 years of age or older. Of the 3 cohorts, the HCV-untreated group had the highest 9-year cumulative incidence of schizophrenia (0.870%, 95% confidence interval [CI] 0.556%–1.311%; p < 0.001); the HCV-treated (0.251%, 95% CI 0.091%–0.599%) and HCV-uninfected (0.118%, 95% CI 0.062%–0.213%) cohorts showed similar cumulative incidence of schizophrenia (p = 0.33). Multivariate Cox analyses showed that HCV positivity (hazard ratio [HR] 3.469, 95% CI 2.168–5.551) was independently associated with the development of schizophrenia. The HCV-untreated cohort also had the highest cumulative incidence of overall mortality (20.799%, 95% CI 18.739%–22.936%; p < 0.001); the HCV-treated (12.518%, 95% CI 8.707%–17.052%) and HCV uninfected (6.707%, 95% CI 5.533%–8.026%) cohorts showed similar cumulative incidence of mortality (p = 0.12).
Limitations: We were unable to determine the precise mechanism of the increased risk of schizophrenia in patients with HCV infection.
Conclusion: In a population-based cohort (most aged ≥ 40 years), HCV positivity was a potential risk factor for the development of schizophrenia; the HCV-associated risk of schizophrenia might be reversed by interferon-based antiviral therapy.
- Received November 1, 2020.
- Revision received July 7, 2021.
- Accepted July 26, 2021.
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/