Hepatitis Linked to Parkinson Disease

Rates of Parkinson disease (PD) are increased following infection with viral hepatitis B and C, according to a new study in Neurology.¹

“We report evidence in favor of elevated rates of subsequent PD in patients with hepatitis B and hepatitis C. Acknowledging constraints of routinely collected data, we suggest that this may reflect factors associated specifically with viral hepatitis or its treatment. We encourage further work confirming this association or contributing insight into potential pathophysiologic pathways, which may be important in understanding the development of PD more broadly,” wrote first author Julia Pakpoor, BA, BM, BCh, of the University of Oxford (Oxford, UK), and colleagues.

The etiology and pathogenesis of PD is complex, perhaps reflecting complicated interactions between genes and environment.  Recently, research has pointed to a role for infection in the development of PD. A series of case reports as well as two epidemiological studies from Taiwan have suggested that hepatitis C, but not hepatitis B, may increase the risk for PD.^2,3

To further investigate the issue, researchers used mortality data linked to the English National Hospital Episode Statistics, which houses inpatient records from all National Health Service hospitals in England. Then they identified incident PD after each of the following conditions: hepatitis B (n=21,633), hepatitis C (n=48,428), autoimmune hepatitis (n=6225), chronic active hepatitis (n=4234) and HIV (n=19,870). To decrease potential bias, they did separate analyses in which they evaluated incident PD at least one year after each of the above diagnoses.

(Continue for key results)

Key Results:

• Increased rates of PD following hepatitis B (standardized rate ratio [RR]: 1.76 (95% confidence interval [CI] 1.28–2.37) (P<0.001)

♦ Similar results for analyses that evaluated incident PD at least one year after hepatitis B (RR 1.82 [1.29–2.5])  

• Increased risk of PD following hepatitis C (RR 1.51 (95% CI, 1.18–1.9) (P<0.001)

♦ Similar results for analyses that evaluated incident PD at least one year after hepatitis B (RR 1.43 [1.09–1.84]) 

• No significant association between PD and autoimmune hepatitis (P=0.087), chronic active hepatitis (P=0.652) or HIV (0.635)

The authors pointed out that explanations for the relationship between viral hepatitis and PD are “highly speculative.” However, they went on to discuss research suggesting that hepatitis C may have neurotropic features, which include the potential for cognitive impairment. Interferon therapy, used in the treatment of chronic hepatitis C, has also been linked to parkinsonism. And parkinsonism seen in liver cirrhosis is thought to be independent of cognitive impairment related to hepatic encephalopathy.

In a linked editorial, Julian Benito-Leon, MD, PhD, of Complutense University (Madrid, Spain) brought up other potential explanations for the relationship. A growing body of research points to neuroinflammation in the etiology of PD, he wrote.⁴ In addition, some evidence suggests that HCV may replicate in the CNS.

“A better understanding of the pathologic bases of PD will lead to advances in the development of more effective treatments. The research by Pakpoor et al. should stimulate more research on how infections, especially virus, may affect the biological processes that lead to PD,” he concluded.

Limitations of the study include the inability to adjust for the prevalence of liver cirrhosis due to lack of available data, so cirrhosis-related parkinsonism cannot be ruled out. Likewise, the study could not control for lifestyle factors like smoking and alcohol. Finally, as a hospital-based study, the results may represent patients at the more severe end of the disease spectrum.

Take-home Points

• A national records study in England found that rates of PD are increased following infection with viral hepatitis B and C, but not autoimmune hepatitis, chronic active hepatitis, or HIV.

• Explanations for the relationship are speculative, but include the sequelae of infection, shared disease mechanisms, and antiviral treatment.

• More research is needed on how infections, particularly viral, play a role in the development of PD.

References:

1. Pakpoor J, et al. Viral hepatitis and Parkinson disease: a national record-linkage study. Neurology. 2017 Mar 29.

2. Tsai HH, et al. Hepatitis C virus infection as a risk factor for Parkinson disease: a nationwide cohort study. Neurology. 2016;86:840-846.

3. Wu WY, et al. Hepatitis C virus infection: a risk factor for Parkinson’s disease. J Viral Hepat. 2015;22:784-791.

4. Benito-León J. Viral hepatitis and the risk of Parkinson disease. Neurology. 2017 Mar 29.