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Can Hepatitis B and C Promote Parkinson Disease?

  • Authors: News Author: Pauline Anderson; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 5/11/2017
  • Valid for credit through: 5/11/2018
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Target Audience and Goal Statement

This article is intended for primary care clinicians, neurologists, infectious disease specialists, gastroenterologists, nurses, and other clinicians who care for patients with chronic viral hepatitis and/or Parkinson disease.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Assess possible mechanisms by which viral hepatitis may influence the risk for Parkinson disease
  • Distinguish diseases of the liver and infectious agents that might increase the risk for Parkinson disease


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  • Pauline Anderson

    Freelance writer, Medscape


    Disclosure: Pauline Anderson has disclosed no relevant financial relationships.


  • Robert Morris, PharmD

    Associate CME Clinical Director, Medscape, LLC


    Disclosure: Robert Morris, PharmD, has disclosed no relevant financial relationships.

CME Author(s)

  • Charles P. Vega, MD

    Health Sciences Clinical Professor, UC Irvine Department of Family Medicine; Associate Dean for Diversity and Inclusion, UC Irvine School of Medicine, Irvine, California


    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: McNeil Consumer Healthcare
    Served as a speaker or a member of a speakers bureau for: Shire Pharmaceuticals

CME Reviewer/Nurse Planner

  • Amy Bernard, MS, BSN, RN-BC

    Lead Nurse Planner, Medscape, LLC


    Disclosure: Amy Bernard, MS, BSN, RN-BC, has disclosed no relevant financial relationships.

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Can Hepatitis B and C Promote Parkinson Disease?

Authors: News Author: Pauline Anderson; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 5/11/2017

Valid for credit through: 5/11/2018


Clinical Context

The etiology of Parkinson disease (PD) has not been elucidated fully and appears to include both genetic and environmental factors. Inflammation in the central nervous system has received increased attention as a part of the pathophysiology of PD, and whether chronic infections can promote PD has been assessed in a limited number of previous studies.

The authors of the current study describe how chronic infection, and infection with hepatitis virus in particular, may promote PD. The neurovascular endothelium demonstrates necessary receptors for hepatitis C virus (HCV), and there have been reports of cognitive impairment associated with chronic HCV infection without other hepatic encephalopathy. HCV was found in a study of human brain tissue samples from infected individuals and was noted to promote dopaminergic neuron cell death in a study of rats.

More importantly, an observational study from Taiwan linked infection with HCV with a higher risk for subsequent PD. The current study by Pakpoor and colleagues seeks to validate this finding using a patient database in England, and the researchers evaluate whether other liver diseases might contribute to the risk for PD.

Study Synopsis and Perspective

Patients with hepatitis B virus (HBV) or HCV may have a significantly increased risk for PD, a new study suggests.

Previous research had tied HCV, but not HBV, 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[ly] 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, Oxford, United Kingdom, told Medscape Medical News.

"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.[1]

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 HBV (21,633 individuals), HCV (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 the 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 after occurrence of HBV was 1.76 (95% confidence interval [CI], 1.28-2.37). The RR of PD after occurrence of HCV 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 HBV and HCV.

Possible Mechanisms

Dr Pakpoor and her colleagues described some possible mechanisms linking hepatitis with PD. They pointed out that all essential HCV 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 HCV found evidence of neuronal toxicity (60% dopaminergic neuron death) induced by the virus in a midbrain neuron-glia co-culture system.

However, Dr Pakpoor stressed that at this stage, pinpointing precise mechanisms linking hepatitis with 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 for development of PD after HCV but not HBV.

It is difficult to say why this research did not link HBV 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 people in the United States have chronic HBV virus infection and 2.7 to 3.9 million people have chronic HCV. Although both conditions can lead to serious illness, many people have few symptoms and do not realize they have the virus, especially at first.

Well Thought Out

In an accompanying editorial,[2] 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 could not 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.

However, 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.

Study Highlights

  • Researchers used the English National Hospital Episode Statistics database to assess their study question. The database contains diagnostic and billing data related to outpatient and inpatient hospital care in England.
  • Patients with a diagnosis code for HBV and HCV infections were compared with a control group who did not have a history of liver disease. Other active comparator groups with control participants included patients with autoimmune hepatitis, chronic active hepatitis, and HIV infection.
  • Patients with a history of PD at the time of assessment were excluded from study analysis.
  • The main study outcome was the association between each of the active illnesses identified and the risk for incident PD. The diagnosis of PD was also assessed with codes from the database.
  • The study cohort included 21,633 patients with HBV infection and 48,428 patients with HCV infection, along with 6225 with autoimmune hepatitis and 4234 with chronic active hepatitis. 19,870 patients in the study had infection with HIV.
  • These patients were compared with 6,132,124 control participants for the risk for incident PD.
  • HBV and HCV infection were significantly associated with the risk for PD. The RR for PD associated with HBV infection was 1.76 (95% CI, 1.28-2.37). The respective RR associated with HCV infection was 1.51 (95% CI, 1.18-1.9).
  • Autoimmune hepatitis, chronic active hepatitis, and HIV infection were not associated with an increased risk for PD.
  • A secondary analysis limited to cases of PD that were diagnosed only after 1 year of study surveillance did not change the principal research results.

Clinical Implications

  • The neurovascular endothelium demonstrates necessary receptors for HCV, and there have been reports of cognitive impairment associated with chronic HCV infection without other encephalopathy. HCV was found in a study of human brain tissue samples and was noted to promote dopaminergic neuron cell death in a study of rats.
  • In the current study by Pakpoor and colleagues, HBV and HCV infection were associated with a higher risk for incident PD, but autoimmune hepatitis, chronic active hepatitis, and HIV infection were not.
  • Implications for the Healthcare Team: The findings of the current study have pathophysiologic and public health significance because they confirm a strong association of HBV and HCV infection with the development of PD. The healthcare team should keep in mind that this may prompt researchers to perform more studies on how virus infections could promote PD.

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