Hepatitis C virus linked to increased risk of Parkinson's disease, studies show

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.

Glossary

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

comorbidity

The presence of one or more additional health conditions at the same time as a primary condition (such as HIV).

stroke

An interruption of blood flow to the brain, caused by a broken or blocked blood vessel. A stroke results in sudden loss of brain function, such as loss of consciousness, paralysis, or changes in speech. Stroke is a medical emergency and can be life-threatening.

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) of 2.50.

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 HR 1.28).

"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.

This analysis 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.

The researchers 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 midbrain.

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."

References

Tsai, HH et al. Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study. Neurology. December 23, 2015 (online before print).

Wu, WY et al. Hepatitis C virus infection: a risk factor for Parkinson's disease. Journal of Viral Hepatitis 22:784-791, 2015.