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

Jur-Shan Cheng; Jing-Hong Hu; Ming-Yu Chang; Ming-Shyan Lin; Hsin-Ping Ku; Rong-Nan Chien; Ming-Ling Chang

doi:10.1503/jpn.200154

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

J Psychiatry Neurosci. 2021 Nov 2;46(6):E583-E591. doi: 10.1503/jpn.200154. Print 2021 Nov-Dec.

Authors

Jur-Shan Cheng¹, Jing-Hong Hu¹, Ming-Yu Chang¹, Ming-Shyan Lin¹, Hsin-Ping Ku¹, Rong-Nan Chien¹, Ming-Ling Chang²

Affiliations

¹ From the Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taiwan (Cheng, Ku); the Department of Emergency Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan (Cheng); the Department of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan (Hu); the Division of Pediatric Neurologic Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan (M.-Y. Chang); the Division of Pediatric General Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan (M.-Y. Chang); the Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital, Taiwan (Lin); the Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (Lin); the Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (Chien, M.-L. Chang); and the Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan (Chien, M.-L. Chang).
² From the Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taiwan (Cheng, Ku); the Department of Emergency Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan (Cheng); the Department of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan (Hu); the Division of Pediatric Neurologic Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan (M.-Y. Chang); the Division of Pediatric General Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan (M.-Y. Chang); the Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital, Taiwan (Lin); the Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (Lin); the Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (Chien, M.-L. Chang); and the Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan (Chien, M.-L. Chang) mlchang8210@gmail.com.

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.

MeSH terms

Adult
Age of Onset
Antiviral Agents / therapeutic use
Cohort Studies
Female
Hepacivirus / pathogenicity*
Hepatitis C / drug therapy
Hepatitis C / epidemiology*
Humans
Incidence
Interferons / therapeutic use
Male
Middle Aged
Schizophrenia / drug therapy
Schizophrenia / epidemiology*
Schizophrenia / virology*
Taiwan / epidemiology
Young Adult

Substances

Antiviral Agents
Interferons