Hepatitis B and C Linked to Parkinson's

Pauline Anderson

March 29, 2017

Patients with hepatitis B or hepatitis C may have a significantly increased risk for Parkinson's disease (PD), a new study suggests.

Previous research had tied hepatitis C, but not hepatitis B, to PD. Results of the new study showed no such relationship with PD among patients with autoimmune hepatitis, chronic active hepatitis, or HIV.

"Clinicians caring for patients with a history of hepatitis B or C should be aware of this seeming increased risk of PD among their patients, so that if neurological symptoms present, these are detected early," lead author, Julia Pakpoor, BA, BM, Bch, Unit of Health Care Epidemiology, Nuffield Department of Population Health, University of Oxford, United Kingdom, told Medscape Medical News.

Dr Julia Pakpoor

"We hope that in the long term, our work will contribute in providing neurologists with a greater understanding of causal pathways in PD."

The study was published online March 29 in Neurology.

For this analysis, the researchers collected data on day-case and inpatient hospital care from the English National Hospital Episode Statistics and, along with mortality data, conducted a retrospective cohort study between 1999 and 2011.

They built cohorts of patients with hepatitis B (21,633 individuals), hepatitis C (48,428), autoimmune hepatitis (6225), chronic active hepatitis (4234), and HIV (19,870).  

They also constructed a reference cohort of 6,132,124 individuals admitted to hospital for a variety of relatively minor medical and surgical conditions — for example, cataract varicose veins, hemorrhoids, bunions, hip replacement, and knee replacement.

From expected and observed numbers of PD cases, they calculated rate ratios (RRs).

The researchers found that the standardized RR of PD following hepatitis B was 1.76 (95% confidence interval [CI], 1.28 - 2.37). The RR of PD following hepatitis C was 1.51 (95% CI, 1.18 - 1.9).

There was no significant elevation of PD rates in the autoimmune hepatitis, chronic active hepatitis, or HIV cohorts. However, the authors noted that the rate of autoimmune hepatitis and PD was "close to reaching statistical significance" in the study.

To reduce possible reverse causality, researchers included only episodes of care for PD first occurring at least 1 year after each exposure condition. That analysis also showed an elevated PD risk after hepatitis B and hepatitis C.

Possible Mechanisms

Dr Pakpoor and her colleagues described some possible mechanisms linking hepatitis to PD. They pointed out that all essential hepatitis C virus receptors are expressed on the brain microvascular endothelium, which constitutes the primary component of the blood-brain barrier. This, they said, suggests one way by which the virus may affect the central nervous system.

In addition, a study in rats with and without hepatitis C found evidence of neuronal toxicity (60% dopaminergic neuron death) induced by the virus in a midbrain neuron–glia coculture system.

But Dr Pakpoor stressed that at this stage, pinpointing precise mechanisms linking hepatitis to PD in humans would be purely speculative.

"We observed significant associations for hepatitis B and C only, but not the other studied exposure diseases," she said. "These findings are therefore likely explained by a specific aspect of viral hepatitis — rather than a general hepatic inflammatory process or general use of antivirals — but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined."

She noted that she and her team did not have detailed clinical data on, for example, medications patients received, symptoms, or genetics.  

Dr Pakpoor hopes follow-up work with different study designs might determine what underlies the observed associations and "shed light on pathophysiological pathways in Parkinson's disease more broadly, which may apply also to patients who do not have hepatitis."

Two earlier studies carried out in Taiwan found an increased risk of developing PD after hepatitis C but not hepatitis B.

It's difficult to say why this research didn't link hepatitis B to PD as did the current study, said Dr Pakpoor. "It could be explained both by differences in study methodology in addition to different ethnic backgrounds of the included populations. It will be very valuable to see if other countries can confirm our findings."

The Centers for Disease Control and Prevention estimates that 850,000 to 2.2 million Americans have chronic hepatitis B virus infection and 2.7 to 3.9 million people have chronic hepatitis C. While both conditions can lead to serious illness, many people have few symptoms and don't realize they have the virus, especially at first.

Well Thought Out

In an accompanying editorial, Julián Benito-León, MD, PhD, Department of Neurology, Complutense University, Madrid, Spain, noted that strengths of the study included its large sample size and "well-thought-out approach to statistical analyses."  

Dr Benito-León also outlined some limitations. For example, the authors couldn't control for lifestyle factors, such as smoking and alcohol intake. As well, using hospital records may have led to exclusion of patients not seeking medical advice, and among those who did, the disorder may have been ascribed incorrectly to other medical conditions.

"The only way to overcome this problem is to use population-based studies where any suspected patients with parkinsonism have a detailed clinical examination," Dr Benito-León writes.

But the authors were aware of the limitations "and, to their credit, provided a thoughtful discussion of these issues," he added.

He told Medscape Medical News that the authors aimed to "mitigate" these limitations the best way they could through the inclusion of a reference cohort, which was also hospital-based.

The new results "are not only confirmatory, but also promising," Dr Benito-León said. The new research "should stimulate more research on how infections, especially virus, may affect the biological processes that lead to PD," he concludes in his editorial.

The study authors and editorialist have disclosed no relevant financial relationships.

Neurology. Published online March 29, 2017. Abstract, Editorial

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