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Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue, and mental health

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Abstract

The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA). Depression, fatigue, and mental health were assessed as patient reported outcomes. At baseline, 54.5% of the patients met the criteria for cognitive impairment and 40% showed impairment in TVA parameters. Follow-up analysis revealed significant improvements in the domains of visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills but not in verbal learning and attention/working memory. We did not observe significant improvement in visual attention measured by TVA. Fatigue and mental health significantly improved at follow-up. Our findings indicate that successful DAA treatment leads to cognitive improvements in several domains measured by standard neuropsychological testing. The absence of improvement in TVA parameters and of significant improvement in the domain of attention/working memory might reflect the persistence of specific cognitive deficits after HCV eradication. In summary, DAA treatment seems to have a positive effect on some cognitive domains and leads to an improvement in mental health and fatigue in HCV-infected patients.

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Acknowledgments

Prof. Dr. med. Wolf Peter Hofmann, Dr. med. Ivanka Krznaric, Andreas Carganico, and Carmen Zedlack for support in patient recruiting.

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Author notes

  1. Felix Kleefeld and Sophie Heller contributed equally to this work

  2. Antje Kraft and Katrin Hahn had an equal contribution

Authors and Affiliations

  1. Department of Neurology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Felix Kleefeld, Sophie Heller, Ute Kopp & Katrin Hahn

  2. Center for Infectiology Berlin, Berlin, Germany

    Patrick Ingiliz

  3. Praxis Jessen2 + Kollegen, Berlin, Germany

    Heiko Jessen

  4. Department of Psychology, University of Copenhagen, Copenhagen, Denmark

    Anders Petersen

  5. Department of Psychiatry, Psychiatric University Hospital St. Hedwig, Charité Universitätsmedizin Berlin, Berlin, Germany

    Antje Kraft

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  1. Felix Kleefeld
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Contributions

Felix Kleefeld, acquisition of data, analysis and interpretation of data, drafting the manuscript

Sophie Heller, acquisition of data, analysis and interpretation of data, drafting the manuscript

Patrick Ingiliz, study concept and design, patient recruiting, revision of manuscript

Heiko Jessen, study concept and design, patient recruiting, revision of the manuscript

Anders Petersen, analysis and interpretation of data, revision of the manuscript

Ute Kopp, study concept and design, revision of the manuscript

Antje Kraft, study concept and design, analysis and interpretation of data, critical revision of manuscript for intellectual content

Katrin Hahn, study concept and design, interpretation of data, study supervision, critical revision of manuscript for intellectual content

Corresponding author

Correspondence to Katrin Hahn.

Ethics declarations

The study followed the ethical principles of the World Medical Association (Declaration of Helsinki) and was approved by the local ethical research committee (reference number: EA1/153/14).

Conflict of interest

Felix Kleefeld reports no conflict of interest.

Sophie Heller reports no conflict of interest.

Patrick Ingiliz has received lecture or consultancy fees from AbbVie, BMS, Gilead, Janssen, and MSD.

Heiko Jessen has received payment for study cost from Gilead Sciences GmbH; for Board membership from Gilead Sciences GmbH, Bioscientia-Institut für Medizinische Diagnostik GmbH, and ViiV Healthcare GmbH; for speaker activities from ViiV Healthcare GmbH, AbbVie Deutschland GmbH & Co. KG, Bristol-Myers Squib GmbH & Co KGaA, Gilead Sciences GmbH, Gilead Sciences Ltd.; and for travel/accommodation/meeting expenses from ViiV Healthcare GmbH, AbbVie Deutschland GmbH & Co. KG, Bristol-Myers Squib GmbH & Co KGaA, Gilead Sciences GmbH, Gilead Sciences Ltd.

Anders Petersen reports no conflict of interest.

Ute Kopp reports no conflict of interest.

Antje Kraft reports no conflicts of interest.

Katrin Hahn has received speaker honoraria or consultancy fees or refunding of conference travel costs from AbbVie, Alnylam, Astellas, CSL Behring, Gilead Sciences GmbH, Pfizer, and ViiV Healthcare GmbH.

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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. J. Neurovirol. 24, 557–569 (2018). https://doi.org/10.1007/s13365-018-0647-z

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