Impact of Hepatitis C Treatment Status on Risk of Parkinson's Disease and Secondary Parkinsonism in the Era of Direct-acting Antivirals

Ranya Selim; Stuart C. Gordon; Yueren Zhou; Talan Zhang; Mei Lu; Yihe G. Daida; Joseph A. Boscarino; Mark A. Schmidt; Sheri Trudeau; Loralee B. Rupp; Humberto C. Gonzalez


J Viral Hepat. 2023;30(6):544-550. 

In This Article

Abstract and Introduction


Research suggests a possible link between chronic infection with hepatitis C virus (HCV) and the development of Parkinson's Disease (PD) and secondary Parkinsonism (PKM). We investigated the impact of antiviral treatment status (untreated, interferon [IFN] treated, direct-acting antiviral [DAA] treated) and outcome (treatment failure [TF] or sustained virological response [SVR]) on risk of PD/PKM among patients with HCV. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we applied a discrete time-to-event approach with PD/PKM as the outcome. We performed univariate followed by a multivariable modelling that used time-varying covariates, propensity scores to adjust for potential treatment selection bias and death as a competing risk. Among 17,199 confirmed HCV patients, we observed 54 incident cases of PD/PKM during a mean follow-up period of 17 years; 3753 patients died during follow-up. There was no significant association between treatment status/outcome and risk of PD/PKM. Type 2 diabetes tripled risk (hazard ratio [HR] 3.05; 95% CI 1.75–5.32; p < .0001) and presence of cirrhosis doubled risk of PD/PKM (HR 2.13, 95% CI 1.31–3.47). BMI >30 was associated with roughly 50% lower risk of PD/PKM than BMI <25 (HR 0.43; 0.22–0.84; p = .0138). After adjustment for treatment selection bias, we did not observe a significant association between HCV patients' antiviral treatment status/outcome on risk of PD/PKM. Several clinical risk factors—diabetes, cirrhosis and BMI—were associated with PD/PKM.


Parkinson's Disease and Secondary Parkinsonism (PD/PKM) are common neurodegenerative disorders, affecting up to 1% of those aged 65–69 and 3% of those ≥80 years.[1] Researchers have projected that prevalence of PD/PKM will increase by 30% by 2030.[1] This includes people infected with hepatitis C virus (HCV). The overall HCV patient population in the United States is ageing, and the group most commonly affected by HCV—the 'Baby Boomer' birth cohort—is reaching their 7th and 8th decades of life. These patients are now surviving longer since the emergence of highly effective direct-acting antiviral (DAA) medications.

The hepatitis C virus is also thought to directly infect the central nervous system (CNS) and studies suggest a possible link between HCV and the development of PD/PKM. Indeed, studies have shown that the virus directly invades neuronal cells, resulting in abnormal neuroimaging as compared to non-hepatitis C subjects.[2,3] A meta-analysis showed that HCV increased risk of PD (odds ratio[OR] = 1.35; 95% confidence interval [CI] 1.19–1.52).[4] One of the included studies also showed that metabolic syndrome was an independent risk factor for PD (OR = 1.42; 95% CI 1.24–1.63).[5] Several studies have reported that successful HCV clearance positively impacts cognitive function and brain metabolism.[6,7] In 2019, two Taiwan-based studies[8,9] showed a reduced risk for PD development among HCV patients treated with interferon (IFN)-based therapy. However, there are no studies assessing the impact of DAA therapies on the risk of PD. Moreover, there is a lack of data on the interplay between cirrhosis—a direct and common complication of HCV—and treatment status on the development of PD/PKM.

An additional limitation of studies of the risk of PD among HCV patients is that they are too often static, based upon patients' characteristics at time of treatment. However, changes in patients' medical condition should be expected over time. For example, an HCV patient without cirrhosis at the time of diagnosis (index date) may become cirrhotic during follow-up, or the patient's treatment status may change (e.g. from untreated to DAA SVR) in the time prior to the development of PD. The inclusion of such 'time-varying' covariates could increase the robustness of PD risk factor analyses.

Using data from the Chronic Hepatitis Cohort Study (CHeCS), an observational study of over 13,000 HCV patients from four large US health systems, we sought to use an extended landmark modelling approach—including not only time-varying covariates, but also time-varying propensity score justification and competing risk factors—to assess the impact of HCV infection and treatment status on risk for development of PD.