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Hepatitis C virus linked to increased risk of Parkinson's disease, studies show
Liz Highleyman, 2016-01-11 08:20:00
People with hepatitis C virus (HCV) infection may be more likely to
develop Parkinson's disease, especially when combined with other risk factors,
though the reason for the association is not fully understood, according to a
pair of recently published studies from Taiwan.
While hepatitis C is primarily a disease of the liver, chronic HCV
infection has also been linked to manifestations throughout the body. Numerous
studies have found associations between HCV infection and various
neuropsychological and cognitive symptoms.
As described in the December 23, 2015, edition of Neurology, Hsin-Hsi Tsai of National Taiwan University
Hospital and colleagues assessed whether HCV
infection is a risk factor for developing Parkinson's disease.
Parkinson's disease is a progressive neurodegenerative
disorder – the second most common after Alzheimer's disease – characterised
by the early death of dopaminergic neurons in the substantia nigra region
of the brain, leading to movement disorders including tremors, muscular
rigidity and gait impairment.
This nationwide population-based
cohort study looked at data from 49,967 people with viral hepatitis –
hepatitis B virus (71%), hepatitis C (21%) or HBV/HCV co-infection (8%) – in
the Taiwan National Health Insurance Research Database, which covers almost all
Taiwanese residents, during the period 2000 to 2010. More than half (57%) were
men and the mean age was about 46 years; blood transfusion was the most common
risk factor for HCV infection. Another 199,868 people without viral hepatitis
served as a control group.
The analysis found that over an
average follow-up period of 12 years, people with hepatitis C were more than
twice as likely to develop Parkinson's disease, with a crude hazard ratio (HR)
After adjusting for age, sex and
co-morbidities including heart disease, stroke, head injury and cirrhosis, the
adjusted HR was 1.29 – about a 30% increased risk – and was statistically
significant. The strongest association was seen
in men, people under age 65 and those with multiple co-morbidities.
In contrast, there was no
significant association between hepatitis B virus infection and Parkinson's
(crude HR 0.66), while people with HBV/HCV co-infection fell in between (crude
"Many factors clearly play a
role in the development of Parkinson's disease, including environmental
factors," said senior author Chia-Hung Kao of China Medical University.
"This nationwide study, using the National Health Insurance Research
Database of Taiwan, suggests that hepatitis caused specifically by the
hepatitis C virus may increase the risk of developing the disease. More
research is needed to investigate this link."
Lead author Tsai suggested that HCV may breach the
blood-brain barrier and enter the central nervous system, where it triggers
inflammation that can cause neuronal injury, possibly including damage to dopaminergic neurons that characterises Parkinson's
disease. Prior studies have suggested that other viruses may also elicit
inflammatory responses in people with Parkinson's. Many experts believe
multiple 'hits' or causal factors combine to cause the disease.
"While these results are intriguing, it is too
early to suggest that people living with hepatitis C should be concerned about
their risk of developing Parkinson's," cautioned Beth Vernaleo of the
Parkinson's Disease Foundation. "That said, this study highlights one
potential risk factor, which should be further investigated."
But another study done in Taiwan, published in the October 2015 Journal of Viral
Hepatitis, found a similar link between HCV
infection and increased risk of Parkinson's disease.
In this study
the researchers analysed data from a community-based screening programme that
included 62,276 participants. They investigated the association between HCV
infection and Parkinson's and also assessed the neurotoxicity of HCV in a rat
midbrain neuron-glial cell culture model.
saw odds ratios similar to the hazard ratios in Tsai's study: 0.62 for hepatitis
B and 1.91 for hepatitis C. After controlling for potential confounding
factors, the association with Parkinson's disease again remained statistically
significant for hepatitis C (adjusted OR 1.39), but not for hepatitis B.
also found that exposure to HCV – but not HBV – led to the death of 60% of
dopaminergic neurons in the rat midbrain. Levels of
inflammatory chemokines such as sICAM-1, LIX/CXCL-5 and RANTES were increased,
while the neuro-protective TIMP-1 was down-regulated in the HCV-infected
In summary, the authors wrote,
"our study not only demonstrated a significantly positive association
between HCV infection and Parkinson's disease
from a large population-based epidemiological study, but also proved the
dopaminergic neuronal toxicity by HCV in vitro at the molecular level through
an increase in cytokines induced by HCV."