Hepatitis C Increases the Risk of Parkinsonism

A large Asian population study supported an association between hepatitis C virus (HCV) infection and parkinsonism in that region, and found that treating HCV reduced the risk of parkinsonism.

In findings presented at the 2018 American Association for the Study of Liver Diseases (AASLD; The Liver Meeting) in San Francisco, Tung-Hung Su, MD, PhD, of the Department of Internal Medicine at the National Taiwan University Hospital and National Taiwan University College of Medicine, and colleagues aimed to investigate the oft-controversially discussed link between HCV and parkinsonism, as well as the effects of antiviral therapy.

The putative association between HCV and Parkinsonism reported in Asian countries has not been found in Western populations. In their study with a large US Medicare database, Zobair Younossi, MD, MPH, and colleagues found no association between the 2 conditions.

The disparate findings notwithstanding, Younossi and colleagues do suggest possible mechanisms for the association, as well as possible reasons for the apparent regional differences. They poined out that HCV is a neurotropic virus and can replicate in the central nervous system, and that some neurotropic viruses such as influenza and coxsackie have been associated with acute and chronic Parkinsonism.

They also consider that differences between population demographics, in the prevalence of HCV, and in the prevalent genotypes could have factored into the different findings.

Su concurred with Younossi on some of the possible reasons for the different findings, in comments to MD Magazine®, including the different HCV genotypes and lower prevalence of HCV infection in the US population.

"The positive association between HCV and Parkinsonism had been validated by another study in Korea, indicating the risk factors of parkinsonism between Asian or US population may be different," Su remarked. "Overall, further large scale studies should be conducted to confirm the association between HCV and parkinsonism."

Su and colleagues compared matched populations of approximately 50,000 patients each with untreated HCV and without HCV, and found the presence of HCV was associated with 31% increased risk of parkinsonism (hazard ratio [HR]: 1.306; 95% confidence interval [CI]: 1.208-1.412), and risk of Parkinsonism requiring medication (adjusted HR: 1.323; 95% CI: 1.214-1.441).

They then matched approximately 23,000 patients with untreated HCV to an HCV population that had been treated with pegylated interferon and ribavirin (PegIFN/RBV). Patients receiving the antiviral therapy had a significantly lower (38%) risk of developing parkinsonism (adjusted HR: 0.618; 95% CI 0.498-0.765), and a reduced risk of Parkinsonism requiring medication (adjusted HR: 0.651; 95% CI: 0.515-0.823).

"Patients with chronic hepatitis C had a significantly higher likelihood of developing Parkinsonism than those without," Su and colleagues reported. "Moreover, Peg IFN/RBV antiviral therapy significantly reduced the risk of Parkinsonism in patients with chronic hepatitis."

The possibility that risk of parkinsonism was reduced with successful treatment of the virus rather than by introduction of the particular antivirals is suggested by a separate observation that interferon can increase risk of parkinsonism through inhibition of the nigrostriatal dopaminergic transmission or induction of neuroinflammation.

Su discussed that putative mechanism with MD Mag, indicating that he finds the data to be equivocal. "These events are rare compared with the large number of interferon therapies, transient, and sometimes the symptoms subsided after interferon discontinuation," Su observed.

In the largest reported series, Su points out that the risk of parkinsonism in interferon-treated patients was approximately one-third of that for those with untreated HCV. Though he acknowledged that duration and interferon type were not specified, and that time-dependent analyses were not applied, he confirmed the results still suggested a protective effect of interferon against parkinsonism development.

"Our study demonstrates the positive association between HCV infection and Parkinsonism," Su emphasized. "Our findings highlight the need for periodical neurological evaluation in patients with chronic hepatitis C for early detection of Parkinsonism."

The study, "Antiviral Therapy is Associated with Reduced Risk of Parkinsonism in Patients with Chronic Hepatitis C," was presented as at the The Liver Meeting 2018.

This article was originally published by MD Magazine.