DAA Therapy May Improve Select Cognitive Domains in HCV-Infected Patients

Successful DAA therapy may lead to cognitive improvement in several domains in HCV-infected patients.

Treatment of hepatitis C virus (HCV)-infected patients with direct-acting antivirals (DAAs) appears to have a positive effect in some cognitive domains, which may lead to an improvement in mental health and fatigue, according to a longitudinal analysis published in the Journal of NeuroVirology.1

Neuroinflammatory processes in patients with HCV suggest a direct central nervous system infection by HCV.2-4 Preliminary data indicates an improvement in cognitive function after DAA therapy.5

In this study, researchers presented complete follow-up data of the cognitive performance of 8 HCV mono-infected patients and 14 HCV/human immunodeficiency virus (HIV) co-infected patients who completed neuropsychological testing at baseline and at week 12 after DAA therapy.1

They found that at baseline, 54.5% of patients met the criteria for cognitive impairment and 40% showed impairment in visual attention parameters. At follow-up, significant improvements in visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills were noted, but not in verbal learning, attention/working memory, and visual attention. However, fatigue and mental health significantly improved.

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The data suggest that successful DAA therapy leads to cognitive improvement in several domains except for visual attention and attention/working memory, which may reflect the continuance of specific cognitive deficits after HCV eradication. 

Future studies are needed to determine whether cognitive deficits in non-cirrhotic HCV-infected patients may represent a new indication for treatment with DAAs.

“DAA treatment leads to an improvement in several cognitive domains measured by standard neuropsychological testing, as well as in fatigue and mental health in both HCV mono-infected and HCV/HIV co-infected patients” stated the study investigators.1

DAAs may have a further advantage to former interferon-based therapies and consideration of neuropsychological impairment may become an important aspect for clinicians when planning HCV treatment regimens.


1. Kleefeld F, Heller S, Ingiliz P, et al. Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue,and mental health [published online May 21, 2018]. J Neurovirol. doi:10.1007/s13365-018-0647-z

2. Fletcher NF, Wilson GK, Murray J, et al. Hepatitis C virus infects the endothelial cells of the blood-brain barrier. Gastroenterology. 2012;142:634-643.

3. Forton DM, Allsop JM, Main J, Foster GR, Thomas HC, Taylor-Robinson SD. Evidence for a cerebral effect of the hepatitis C virus. Lancet. 2001;358:38-39.

4. Weissenborn K, Krause J, Bokemeyer M, et al. Hepatitis C virus infection affects the brain-evidence from psychometric studies and magnetic resonance spectroscopy. J Hepatol. 2004;41:845-851.

5. Kleefeld F, Heller S, Jessen H, Ingiliz P, Kraft A, Hahn K. Effect of interferon-free therapy on cognition in HCV and HCV/HIV infection: a pilot study. Neurology. 2017;88:713-715.