Association between hepatitis C virus infection and Parkinson's disease

Hepatitis C virus (HCV)-induced neuroinflammation may lead to dopaminergic neuronal loss, suggesting a possible association between HCV infection and Parkinson’s disease (PD). To date, there are two Taiwanese studies using community-based data that showed an increased PD risk by around 2-fold with HCV infection. We investigated the association between HCV infection and PD through a hospital-based, case-control study. The study sample comprised 1,558 PD patients and 1,558 ageand sex-matched controls—randomly selected from 70,926 health-check examinees (Supporting Data). Overall anti-hepatitis C virus antibody (anti-HCV) prevalence in the PD group was significantly higher than that in the control group (Fig. 1). Anti-HCV positivity was significantly associated with PD for overall age groups. In elderly subjects 70 years, a significant association between anti-HCV positivity and PD was observed; however, in younger subjects, the association was not noted. In contrast, the association between hepatitis B surface antigen (HBsAg) and PD was not observed for overall age groups; however, in elderly subjects, HBsAg positivity was negatively associated with PD. The difference of anti-HCV positivity between age groups may be attributed to lower prevalence of HCV infection, as well as PD, in younger subjects. However, the Taiwanese study showed a significant association in those younger than 65 years. This may be attributed to different prevalence and risk factors of HCV infection between the two countries. In the Korean population, anti-HCV prevalence increases with age, and there are only a few intravenous drug users among anti-HCV-positive subjects. Further studies in other populations are needed to firmly establish the association between HCV infection and PD. Among the 27 anti-HCV-positive PD cases, detection of anti-HCV positivity anteceded the diagnosis of PD by 4.7 6 3.4 years in 13 patients, whereas anti-HCV positivity was concomitantly detected at the time of PD diagnosis in the other 14 patients. Among the 27 patients, 15 exhibited no clinical evidence of liver disease, and in 9 patients who underwent the HCV RNA test, 4 showed negativity, suggesting that even remote exposure to HCV without severe liver damage may be associated with PD. A recent study showed immune crossreactive potential of viral peptides, including HCV, which was shared with human brain antigens associated with neurodegenerative disorders. Further studies investigating the pathomechanism of the association between HCV and PD are needed. Our study had several limitations. First, given the crosssectional design of this study, it was not possible to determine the temporal sequence of HCV infection and onset of PD. Second, anti-HCV-positive subjects may seek medical services more frequently, which may increase the chance of PD diagnosis. However, the number of physician visits did not differ between anti-HCV-positive and -negative patients (Supporting Table 5). Third, besides age and sex, there may be other factors related to HCV infection, confounding the association between HCV infection and PD. Finally, the number of anti-HCV-positive subjects was small, particularly for the age-stratified analysis; thus, future prospective and longitudinal studies including more subjects are necessary. In conclusion, HCV infection was significantly associated with PD.