Chronic Hepatitis C Virus Infection Tied to Parkinson Disease

What connection between HCV and Parkinson disease?

Chronic hepatitis C virus (HCV) infection is tied to an increased risk of Parkinson disease (PD), according to results of a new study. Individuals with chronic HCV who were treated with interferon-based therapy had a lower risk of PD vs untreated individuals.¹

The results, published in JAMA Neurology, may add PD to the list of extrahepatic complications that stem from chronic HCV infection including renal disease, type 2 diabetes, coronary artery disease, lymphoma, and skin and blood disorders.

These complications highlight the importance of early recognition of HCV in primary care and, when necessary, referral for treatment.

“To our knowledge, this is the first cohort study to investigate the association between antiviral therapy and risk of PD in patients with chronic HCV infection,” wrote researchers led by Wey-Yil Lin, MD, Department of Neurology, Chang Gung Memorial Hospital in Taoyuan, Taiwan. “The results demonstrated a reduced incidence of PD in patients who received interferon-based antiviral treatment. The reduction appeared obvious at 5 years after antiviral therapy and became more statistically significant at the end of follow-up,” researchers added.

“The lower rate of PD occurrence in the treated patients may suggest that HCV infection is a risk factor for PD development, and antiviral therapy lowers the risk.”

Researchers analyzed claims data from the Taiwan National Health Insurance Research Database, which insures up to 99% of the Taiwanese population (about 23.5 million people). The study included adult patients with a new HCV diagnosis who received anti-PD medications between January 2003 and December 2013.

Next: PD risk lower at 5 years

The analysis included 188 152 adults aged >20 years, of which an equal number of patients (39 939) received either interferon-based therapy for HCV or did not. Treated individuals received antivirals for anywhere from 16 to 48 weeks.

Study authors used propensity score matching to adjust for baseline differences between the 2 groups. Results were adjusted for comorbidities associated with HCV infection and a range of factors that could affect risk for PD, such as head injury.

The risk for PD was not significantly different between the untreated and treated groups after 1 year (p=0.39) and 3 years (p=0.22) of follow-up.

However, after 5 years of follow-up, the risk of PD was significantly lower by about 25% in the treated group vs the untreated group (HR, 0.75; 95% CI, 0.59-0.96, p=0.02). Risk of PD remained significantly lower until the end of follow-up in the untreated group (HR, 0.71; 95% CI, 0.58-0.87, p=0.001).

In a linked editorial,² Adolfo Ramirez-Zamora, MD, Christopher W. Hess, MD, and David R. Nelson, MD, all from the University of Florida at Gainesville, noted several mechanisms that could explain these results, including immunologic mechanisms and neuroinflammation caused by HCV entry into the brain.

“While the search for a disease-modifying or neurorestorative therapies for PD continues, identification of potentially treatable PD risk factors presents a unique opportunity for treatment. Additional studies with detailed viral analysis and exposure are needed, including in other geographic and ethnic distributions,” the editorial writers concluded.

They also mentioned several limitations of the study. Because the database lacked data on viral profiles, researchers could not evaluate whether severity of HCV infection is linked to PD. They also could not assess newer direct acting antivirals, as well as some variables that may affect risk for PD (eg, smoking, consumption of coffee or alcohol). Finally,

PD is a slowly progressive condition, and the study may not have been long enough to capture all cases of PD.

References:

1. Lin WY, Lin MS, Weng YH, et al. Association of antiviral therapy with risk of Parkinson disease in patients with chronic hepatitis C virus infection. JAMA Neurol. 2019 Jun 5. doi: 10.1001/jamaneurol.2019.1368. (Full text)

2. Ramirez-Zamora A, Hess CW, Nelson DR. Is interferon therapy for hepatitis C infection a treatable risk factor for Parkinson disease? [editorial] JAMA Neurol. 2019 Jun 5. doi: 10.1001/jamaneurol.2019.1377.