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Persistent neurocognitive decline in a clinic sample of hepatitis C virus-infected persons receiving interferon and ribavirin treatment

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Abstract

Treatment of hepatitis C virus (HCV) with pegylated interferon and ribavirin (IFN/RBV) can be associated with neuropsychiatric side effects, which may necessitate dose reductions or treatment discontinuation. This study aimed to characterize the time course and predictors of cognitive and affective/mood symptoms after IFN/RBV treatment initiation. Forty individuals enrolled in a longitudinal project underwent comprehensive cognitive, medical, and psychiatric assessment at baseline and 10 weeks, 6 months, 12 months, and 18 months after treatment initiation. Analyses were conducted to determine the prevalence of neurocognitive impairment over time; explicate the relationship between neurocognitive impairment, neuropsychiatric symptoms, and liver disease at each time point; and identify predictors of neurocognitive decline as well as cognitive effects of viral clearance. By 10 weeks after initiating IFN/RBV, the prevalence of neurocognitive impairment rose from 22.5 to 47.4 % (p < 0.05). Infection with genotype 1 and premorbid depression were associated with more severe declines (p < 0.05). After 18 months, 42.5 % remained neurocognitively impaired, independent of viral clearance, severity of liver disease, and current depressive symptoms. Undetectable viral load was not associated with improvement 18 months after initiating treatment (p > 0.10). Results of the current study indicate that IFN/RBV treatment-emergent neurocognitive declines are significant, prevalent, and may persist long after treatment cessation. Clinicians should monitor cognition throughout the course of treatment for HCV, noting that early declines may indicate individuals at elevated risk for persistent neurocognitive impairment. Longer-term studies are needed to determine whether lasting declines may remit over longer intervals or with newer direct acting agents.

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Abbreviations

HCV:

Hepatitis C virus

IFN/RBV:

Interferon and ribavirin

CNS:

Central nervous system

NIDA:

National Institute on Drug Abuse

UCSD:

University of California San Diego

IgG:

Immunoglobulin G

ELISA:

Enzyme-linked immunosorbent assay

HIV:

Human immunodeficiency virus

MDD:

Major depressive disorder

GDS:

Global deficit score

SD:

Standard deviation

BDI-II:

Beck Depression Inventory-II

APRI:

Aspartate aminotransferase to platelet ratio index

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Acknowledgments

The Translational Methamphetamine AIDS Research Center (TMARC) is supported by Center award P50DA026306 from the National Institute on Drug Abuse (NIDA) and is affiliated with the University of California, San Diego (UCSD) and the Sanford-Burnham Medical Research Institute (SBMRI). The TMARC comprised the following: Director— Igor Grant, M.D.; Co-Directors —Ronald J. Ellis, M.D., Ph.D., Cristian L. Achim, M.D., Ph.D., and Scott L. Letendre, M.D.; Center Manager—Steven Paul Woods, Psy.D.; Assistant Center Manager—Aaron M. Carr, B.A.; Clinical Assessment and Laboratory (CAL) Core: Scott L. Letendre, M.D. (Core Director), Ronald J. Ellis, M.D., Ph.D., Rachel Schrier, Ph.D.; Neuropsychiatric (NP) Core: Robert K. Heaton, Ph.D. (Core Director), J. Hampton Atkinson, M.D., Mariana Cherner, Ph.D., Thomas D. Marcotte, Ph.D., Erin E. Morgan, Ph.D.; Neuroimaging (NI) Core: Gregory Brown, Ph.D. (Core Director), Terry Jernigan, Ph.D., Anders Dale, Ph.D., Thomas Liu, Ph.D., Miriam Scadeng, Ph.D., Christine Fennema-Notestine, Ph.D., Sarah L. Archibald, M.A.; Neurosciences and Animal Models (NAM) Core: Cristian L. Achim, M.D., Ph.D. (Core Director), Eliezer Masliah, M.D., Stuart Lipton, M.D., Ph.D.; Administrative Coordinating Core (ACC)—Data Management and Information Systems (DMIS) Unit: Anthony C. Gamst, Ph.D. (Unit Leader), Clint Cushman (Unit Manager); ACC—Statistics Unit: Ian Abramson, Ph.D. (Unit Leader), Florin Vaida, Ph.D., Reena Deutsch, Ph.D., Anya Umlauf, M.S.; ACC—Participant Unit: J. Hampton Atkinson, M.D. (Unit Leader), Jennifer Marquie-Beck, M.P.H. (Unit Manager); Project 1: Arpi Minassian, Ph.D. (Project Director), William Perry, Ph.D., Mark Geyer, Ph.D., Brook Henry, Ph.D.; Project 2: Amanda B. Grethe, Ph.D. (Project Director), Martin Paulus, M.D., Ronald J. Ellis, M.D., Ph.D.; Project 3: Sheldon Morris, M.D., M.P.H. (Project Director), David M. Smith, M.D., M.A.S., Igor Grant, M.D.; Project 4: Svetlana Semenova, Ph.D. (Project Director), Athina Markou, Ph.D., James Kesby, Ph.D.; Project 5: Marcus Kaul, Ph.D. (Project Director). The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Government. We have no commercial affiliations or consultancies which might be construed as conflicts of interest. Financial support: NIH (P50-DA026306), P01 DA12065, P30-MH062512.

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Authors and Affiliations

  1. University of California, San Diego, Translational Methamphetamine AIDS Research Center, San Diego, CA, USA

    Jordan E. Cattie

  2. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA

    Steven Paul Woods, William Perry, Mariana Cherner, Anya Umlauf, Donald Franklin & Robert K. Heaton

  3. Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    Scott L. Letendre, Fatma Barakat & Tarek Hassanein

  4. Department of Psychiatry, University of California, San Diego, Translational Methamphetamine AIDS Research Center, La Jolla, CA, 92093-0603, USA

    Igor Grant

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  1. Jordan E. Cattie
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  2. Scott L. Letendre
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  3. Steven Paul Woods
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  4. Fatma Barakat
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  5. William Perry
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  11. Igor Grant
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The Translational Methamphetamine AIDS Research Center (TMARC) Group

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Correspondence to Igor Grant.

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Cattie, J.E., Letendre, S.L., Woods, S.P. et al. Persistent neurocognitive decline in a clinic sample of hepatitis C virus-infected persons receiving interferon and ribavirin treatment. J. Neurovirol. 20, 561–570 (2014). https://doi.org/10.1007/s13365-014-0265-3

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