Hepatitis C-associated late-onset schizophrenia: a nationwide, population-based cohort study

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.

Figure 1

Flow chart of Taiwan National Health Insurance Research Database study sample selection. HBV = hepatitis B virus; HCV = hepatitis C virus; HSV = herpes simplex virus; PEG-IFN: pegylated interferon; PS = propensity score.

Figure 2

Cumulative incidence of schizophrenia among the 3 Taiwan National Health Insurance Research Database cohorts: HCV-treated, HCV-untreated and HCV-uninfected. HCV = hepatitis C virus.

Figure 3

Forest plot of factors associated with incident schizophrenia in the 2 Taiwan National Health Insurance Research Database cohorts: HCV-positive (HCV-untreated) and HCV-negative (combination of HCV-treated and HCV-uninfected). CCI = Charlson Comorbidity Index score; HCL = higher confidence interval limit; HCV = hepatitis C virus; HR = hazard ratio; LCL = lower confidence interval limit.