Epidemiology has tied infection with hepatitis C to an increased risk for Parkinson’s disease. But what happens when the infection is treated? By surveying medical records of nearly 200,000 patients, researchers led by Ying-Zu Huang and Rou-Shayn Chen, Chang Gung Memorial Hospital, Taoyuan, Taiwan, concluded that giving people interferon for hepatitis C virus (HCV) infection lowers their risk of subsequently developing this neurodegenerative disease. Published June 5 in JAMA Neurology, the paper does not establish cause and effect but, all the same, it argues that HCV infection may be a modifiable risk factor for PD.
- Treating hepatitis C lowers rates of future Parkinson’s.
- The virus might be a modifiable risk factor for PD.
- Supports emerging evidence that infections contribute to neurodegeneration.
Chronic HCV infection is a major cause of disease worldwide, leading to inflammation, cirrhosis, even cancer of the liver. HCV affects other organs, too, raising the risk of diabetes, cardiovascular disease, and stroke. Multiple epidemiological studies suggest a link between HCV and Parkinson’s, and a recent meta-analysis indicated that people with chronic HCV have 1.35 times the risk of uninfected people (Wijarnpreecha et al., 2018).
To explore the influence of treatment, the researchers examined data from 23.5 million people in the Taiwan national health system, which covers 99 percent of the population. Led by first author Wey-Yil Lin, the investigators identified 188,152 new diagnoses of HCV between 2003, the year the health service began paying for interferon therapy, and 2013. Of those, nearly 40,000 were treated with a combination of interferon α2b and ribavirin for 16 to 48 weeks. Interferons boost anti-viral immunity, while ribavirin is a nucleoside analog that interferes with virus replication and enhances the immune response. The researchers matched each treated patient with an untreated infected person similar in age, sex, comorbidities, and medication history, and determined how many in each group developed PD at one, three, five, and 10 years after diagnosis or start of HCV treatment.
Overall, 39 percent more people in the untreated group developed PD than in the treated group. Over time, incidence rose in both, but more slowly in the treated group. After five years, treated patients showed a statistically significant, 25 percent lower risk of PD, which widened to 29 percent at 10 years.
How to explain this? Unfortunately, the investigators were unable to access information from the medical records about virus load or liver function, and therefore did not determine if the incidence of PD tracked with viral clearance or liver health. Interferon might act by modulating the immune system, reducing inflammation, or clearing the virus altogether. Treatment reduced but did not eliminate PD risk, suggesting that HCV is but one risk factor among many.
In an accompanying editorial, Adolfo Ramirez-Zamora and colleagues at University of Florida, Gainesville, write that interferon has extensive immunomodulatory effects, while modestly boosting viral clearance. “Additional studies with detailed viral analysis and exposure are needed, including in other geographic and ethnic distributions,” they wrote. The study did not analyze patients treated with the newer HCV medications, which directly target viral replication and infection and cure most people of HCV.
Meanwhile, researchers are paying attention to links between infectious organisms and neurodegenerative disease more broadly. On June 24, a workshop in Quebec City will focus on the role of human herpesviruses in Alzheimer’s. It follows on recent work correlating viral loads with amyloid pathology (May 2019 news; Jun 2018 news; Jun 2018 news). In addition, the Infectious Diseases Society of America this week announced five research grants worth $100,000 each for studies to identify microbial triggers for neurodegeneration. Applications will be accepted through November 30.—Pat McCaffrey
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- Wijarnpreecha K, Chesdachai S, Jaruvongvanich V, Ungprasert P. Hepatitis C virus infection and risk of Parkinson's disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018 Jan;30(1):9-13. PubMed.
- Lin WY, Lin MS, Weng YH, Yeh TH, Lin YS, Fong PY, Wu YR, Lu CS, Chen RS, Huang YZ. Association of Antiviral Therapy With Risk of Parkinson Disease in Patients With Chronic Hepatitis C Virus Infection. JAMA Neurol. 2019 Jun 5; PubMed.
- Ramirez-Zamora A, Hess CW, Nelson DR. Is Interferon Therapy for Hepatitis C Infection a Treatable Risk Factor for Parkinson Disease?. JAMA Neurol. 2019 Jun 5; PubMed.