Literature Review

Treatment for hepatitis C reduces risk of Parkinson’s disease

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Results may present a unique opportunity for treatment

The findings of Lin et al. suggest a potentially modifiable hepatologic risk factor for Parkinson’s disease, Adolfo Ramirez-Zamora, MD, associate professor of neurology; Christopher W. Hess, MD, assistant professor of neurology; and David R. Nelson, MD, senior vice president for health affairs, all at the University of Florida in Gainesville, wrote in an accompanying editorial. Hepatitis C virus infection might enter the brain through the microvasculature and might induce microglial and macrophage-related inflammatory changes (JAMA Neurol. 2019 June 5. doi: 10.1001/jamaneurol.2019.1377).

Lin et al. estimated high diagnostic accuracy for Parkinson’s disease in their study. Nevertheless, clinical, neuroimaging, and pathological confirmation was unavailable, which is a limitation of their investigation, said Dr. Ramirez-Zamora and colleagues. “The diagnosis of Parkinson’s disease in early stages can be challenging, as other related conditions can mimic Parkinson’s disease, including cirrhosis-related parkinsonism. Moreover, using record-linkage systems excludes patients who did not seek medical advice or those who were misdiagnosed by symptoms alone, which may also underestimate the prevalence of Parkinson’s disease. Using population-based studies would be a more accurate method.”

Because interferon, which was the antiviral therapy used in this study, greatly affects the immune system and has a modest rate of eradicating viral hepatitis C infection, future research should examine the association between Parkinson’s disease and patients who cleared the virus, as well as patients who did not, said Dr. Ramirez-Zamora and colleagues. Such research could shed light on potential mechanisms of treatment response. Lin et al. did not examine the newer direct-acting antiviral therapies for hepatitis C virus infection, which cure more than 90% of patients. Nor did they analyze other well established lifestyle and demographic risk factors for developing the disease. In addition, “the authors could not generalize the results to those aged 75 years or older because of the substantially smaller number of patients in this age group,” said Dr. Ramirez-Zamora and colleagues.

Still, “identification of potentially treatable Parkinson’s disease 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,” they concluded.



Among patients with hepatitis C virus, antiviral treatment is associated with a reduced risk of Parkinson’s disease, according to a cohort study published online June 5 in JAMA Neurology. The results provide evidence that hepatitis C virus is a risk factor for Parkinson’s disease.

In the past several years, epidemiologic studies have suggested an association between hepatitis C virus infection and Parkinson’s disease. A study published in 2017, however, found no association between the two. In addition, these investigations did not consider antiviral therapy as a potential modifying factor.

Wey-Yil Lin, MD, a neurologist at Landseed International Hospital in Taoyuan, Taiwan, and colleagues examined claims data from the Taiwan National Health Insurance Research Database to identify the risk of incident Parkinson’s disease in patients with hepatitis C virus infection who received antiviral treatment, compared with those who did not receive treatment.

The investigators selected all patients with a new diagnosis of hepatitis C virus infection with or without hepatitis from January 1, 2003, to December 31, 2013. They excluded patients who were aged 20 years or younger; had Parkinson’s disease, dementia, or stroke; or had had major hepatic diseases on the index date. To ensure that treated patients had had an effective course of therapy, the researchers excluded patients who were lost to follow-up within 6 months of the index date, received antiviral therapy for fewer than 16 weeks, or developed Parkinson’s disease within 6 months of the index date.

The primary outcome was incident Parkinson’s disease. Dr. Lin and colleagues excluded participants with a diagnosis of stroke and dementia before the index date to reduce the possibility of enrolling participants with secondary and atypical parkinsonism.

To minimize the potential selection bias to which observational studies are subject, the investigators performed propensity score matching with sex, age, comorbidities, and medication as covariates. This method was intended to create treated and untreated cohorts with comparable characteristics.

Dr. Lin and colleagues included 188,152 patients in their analysis. After matching, each group included 39,936 participants. In the group that received antiviral treatment, 45.0% of participants were female, and mean age was 52.8 years. In the untreated group, 44.4% of participants were female, and mean age was 52.5 years.

The incidence density of Parkinson’s disease per 1,000 person-years was 1.00 in the treated group and 1.39 in the untreated group. The difference in risk of Parkinson’s disease between the treated and untreated groups was statistically significant at year 5 of follow-up (hazard ratio [HR], 0.75) and at the end of the cohort (HR, 0.71). The risk did not differ significantly at year 1 and year 3, however. A subgroup analysis found a greater benefit of antiviral therapy among patients who concurrently used dihydropyridine calcium channel blockers.

“To our knowledge, this is the first cohort study to investigate the association between antiviral therapy and risk of Parkinson’s disease in patients with chronic hepatitis C viral infection,” said Dr. Lin and colleagues. Although it is possible that interferon-based antiviral therapy directly protected against the development of Parkinson’s disease, the short time of exposure to the antiviral agent “makes protecting against Parkinson’s disease development in 5 years less likely,” they added.

Among the study limitations that the authors acknowledged was the lack of data about hepatic function profile, serum virologic response, viral genotype, and hepatitis C virus RNA-level. The database that the investigators used also lacked data about behavioral factors (e.g., smoking status, coffee consumption, and alcohol consumption) that may have affected the incidence of Parkinson’s disease in the cohort. Investigations with longer follow-up periods will be needed to provide clearer information, they concluded.

The authors reported no conflicts of interest. The study was funded by grants from Chang Gung Medical Research Fund and from Chang Gung Memorial Hospital.

SOURCE: Lin W-Y et al. JAMA Neurol. 2019 Jun 5. doi: 10.1001/jamaneurol.2019.1368.

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