Hepatitis C Treatment and Parkinson’s Risk
Posted on: Friday, June 7, 2019 By: KorchekStaff
Taiwanese study of insurance claims yields surprise, and a puzzle
Patients with hepatitis C virus (HCV) treated with interferon-α-2b and ribavirin appeared to have a lower risk of Parkinson's disease than untreated patients, a retrospective insurance claims analysis in Taiwan found.
HCV therapy (not including newer direct-acting antiviral agents) was tied to a significant reduction in Parkinson's at 5-year follow-up and increased to the end of the follow-up period which was a maximum of 11 years, reported Ying-Zu Huang, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues in JAMA Neurology and presented simultaneously at the World Parkinson Congress in Kyoto, Japan.
"The results seem to support the theory that HCV infection is a risk factor for developing Parkinson's disease," they wrote. "Antiviral therapy has shown potential in lowering this risk."
Earlier research in Taiwan showed HCV patients had significantly increased risk of developing Parkinson's disease, but a study of Medicare recipients showed no link between the two in the U.S. A five-study meta-analysis published last year found a higher risk of Parkinson's disease among HCV-infected patients. But none of these studies looked at HCV treatment.
In this analysis, Huang and colleagues assessed 188,152 adults with a new HCV diagnosis from 2003 to 2013 in the Taiwan National Health Insurance research database, excluding people with an established history of severe liver disease, stroke, dementia, or Parkinson's. They categorized patients into treated and untreated groups depending on whether they received interferon-based antiviral therapy, then used propensity score matching to balance sex, age, comorbidities, and medications in two groups of 39,936 people each.
HCV therapy was a combination of pegylated interferon α-2b and ribavirin ranging from 16 to 48 weeks (direct-acting antivirals were not available in Taiwan's national health insurance during the study period). Patients were an average age of around 53 when treatment started and 55% were men.
The researchers defined the number of people with Parkinson's as the event number, and the proportion of event number in the cohort as the event rate. Because observation periods differed among patients, they used incidence density -- the event number divided by the sum of the observed duration of each participant, shown as a number per 1,000 person-years after the index date -- as an estimate of incidence rate.
After propensity score matching, the incidence density of Parkinson's disease was 1.00 (95% CI 0.85-1.15) in the treated group and 1.39 (95% CI 1.21-1.57) per 1,000 person-years in the untreated group.
At year 5 of follow-up, the risk of Parkinson's between the two groups was statistically significantly different (HR 0.75; 95% CI 0.59-0.96), which continued until the study's maximal follow-up at 11 years (HR 0.71; 95% CI 0.58-0.87). At year 1 and year 3, the risk was not different, the authors said.
In both groups, the event number and incidence density of Parkinson's rose gradually over the years, but the event rate in the treated group increased more slowly (from 3.03 per 1,000 to 4.06 per 1,000) than in the untreated group (from 3.93 per 1,000 to 5.51 per 1,000).
This study may point to a potentially treatable risk factor for Parkinson's development, observed Adolfo Ramirez-Zamora, MD, of the University of Florida, and co-authors in an accompanying editorial. The findings add to evolving knowledge about immunological and infectious factors in Parkinson's and "suggest mechanisms that may be responsible for this association, including neuroinflammation and clearance of HCV infection," the editorialists wrote.
Pathogenic mechanisms between HCV infection and Parkinson's aren't known, but "it is possible that HCV infection enters the brain through the microvasculature and then induces microglial and macrophages inflammatory changes, with damage associated with the release of neurotoxins such as nitric oxide and proinflammatory cytokines, including tumor necrosis factor, IL-1, and IL-6.10," Ramirez-Zamora and colleagues added.
The study had several limitations, Huang and co-authors noted: it did not assess newer antiviral therapies, the severity of HCV, or lifestyle risk factors for Parkinson's. It also could not draw conclusions about people ages 75 and older because very few treated patients were in this age group. Because Parkinson's is a slow, progressive disorder, a maximum 11-year follow-up period was not long enough to observe the course of infection, inflammation, or treatment, they said.