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The impact of human immune deficiency virus and hepatitis C coinfection on white matter microstructural integrity

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Abstract

The purpose of the present study is to examine the integrity of white matter microstructure among individuals coinfected with HIV and HCV using diffusion tensor imaging (DTI). Twenty-five HIV+ patients, 21 HIV+/HCV+ patients, and 25 HIV− controls were included in this study. All HIV+ individuals were stable on combination antiretroviral therapy (cART; ≥3 months). All participants completed MRI and neuropsychological measures. Clinical variables including liver function, HIV-viral load, and CD4 count were collected from the patient groups. DTI metrics including mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) from five subregions of the corpus callosum were compared across groups. The HIV+/HCV+ group and HIV+ group were similar in terms of HIV clinical variables. None of the participants met criteria for cirrhosis or fibrosis. Within the anterior corpus callosum, significant differences were observed between both HIV+ groups compared to HIV− controls on DTI measures. HIV+ and HIV+/HCV+ groups had significantly lower FA values and higher MD and RD values compared to HIV− controls; however, no differences were present between the HIV+ and HIV+/HCV+ groups. Duration of HIV infection was significantly related to DTI metrics in total corpus callosum FA only, but not other markers of HIV disease burden or neurocognitive function. Both HIV+ and HIV+/HCV+ individuals had significant alterations in white matter integrity within the corpus callosum; however, there was no evidence for an additive effect of HCV coinfection. The association between DTI metrics and duration of HIV infection suggests that HIV may continue to negatively impact white matter integrity even in well-controlled disease.

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References

  • Analyze imaging software, version 11.0. AnalyzeDirect

  • Basser PJ, & Pierpaoli C (1996) Microstructural features measured using diffusion tensor imaging. J Magn Reson B 111(3):209–219

  • Carvalho-Filho RJ, Schiavon LL, Narciso-Schiavon JL (2008) Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co-infection. Liver Int 28(4):486–493. doi:10.1111/j.1478-3231.2008.01675.x

    Article  CAS  PubMed  Google Scholar 

  • Chang L, Wong V, Nakama H et al (2008) Greater than age-related changes in brain diffusion of HIV patients after 1 year. J of Neuroimmune Pharm 3:265–274. doi:10.1007/s11481-008-9120-8

    Article  Google Scholar 

  • Chanraud S, Zahr N, Sullivan E,P, Fefferbausm A (2010) MR diffusion tensor imaging: a window into white matter integrity of the working brain. Neuropsychol Rev 20(2):209–255

    Article  PubMed  PubMed Central  Google Scholar 

  • Cherner M, Letendre S, Heaton RK (2005) Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology 64(8)):1343–347. doi:10.1212/01.WNL.0000158328.26897.0D

    Article  CAS  PubMed  Google Scholar 

  • Ciccarelli N, Fabbiani M, Grima P et al (2013) Comparison of cognitive performance in HIV or HCV mono-infected and HIV–HCV co-infected patients. Infection 41(6):1103–1109

    Article  CAS  PubMed  Google Scholar 

  • Clifford DB, Smurzynski M, Park LS et al (2009) Effects of active HCV replication on neurologic status in HIV RNA virally suppressed patients. Neurology 73(4):309–314. doi:10.1212/WNL.0b013e3181af7a10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clifford DB, Vaida F, Kao YT, Franklin DR, Letendre SL, Collier AC, Teshome M (2015) Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people. Neurology 84(3):241–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crystal H, Kleyman I, Anastos K et al (2012) Effects of hepatitis C and HIV on cognition in women: data from the women's interagency HIV study. J of Acquir Immune Defic Syndr 59(2):149–154

    Article  Google Scholar 

  • El Rihim AYA, Omar RF, Fathalah W, El Attar I, Hafez HA, Ibrahim W (2013) Role of fibroscan and APRI in detection of liver fibrosis: a systematic review and meta-analysis. Arab Journal of Gastroenterology 14(2):44–50

    Article  Google Scholar 

  • Filippi CG, Ulug AM, Ryan E et al (2001) Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. AJNR Am J Neuroradiol 22(2):277–283

    CAS  PubMed  Google Scholar 

  • Forton DM, Thomas HC, Taylor-Robinson SD (2004) Central nervous system involvement in hepatitis C virus infection. Metab Brain Dis 19(3–4):383–391

    Article  PubMed  Google Scholar 

  • Gess, M., & Forton, D. (2012). Effect of hepatitis C virus on the central nervous system of HIV-infected individuals. Virus Adaptation & Treatment, 4

  • Gladsjo JA, Schuman CC, Evans JD et al (1999) Norms for letter and category fluency: demographic corrections for age, education, and ethnicity. Assessment 6(2):147–178

    Article  CAS  PubMed  Google Scholar 

  • SA Glantz, Primer of Biostatistics, 2005, ISBN = 978-0071435093

  • Gongvatana A, Cohen RA, Correia S et al (2011) Clinical contributors to cerebral white matter integrity in HIV-infected individuals. J of neurovirology 17(5):477–486

    Article  Google Scholar 

  • Heaton, R. K., Grant, I., & Matthews, C. G. (1991). Comprehensive norms for an expanded Halstead-Reitan Battery: Demographic corrections, research findings, and clinical applications. Odessa, FL: Psychological Assessment Resources

  • Hilsabeck RC, Hassanein TI, Carlson MD et al (2003) Cognitive functioning and psychiatric symptomatology in patients with chronic hepatitis C. J Int Neuropsychol Soc 9(6):847–854. doi:10.1017/S1355617703960048S1355617703960048

    Article  PubMed  Google Scholar 

  • Hofer S, Frahm J (2006) Topography of the human corpus callosum revisited—comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage 32(3):989–994

    Article  PubMed  Google Scholar 

  • Jernigan TL, Archibald SL, Fennema-Notestine C et al (2011) Clinical factors related to brain structure in HIV: the CHARTER study. J of Neurovirology 17:248–257. doi:10.1007/s13365-011-0032-7

    Article  Google Scholar 

  • Kallianpur KJ, Kirk GR, Sailasuta N et al (2012) Regional cortical thinning associated with detectable levels of HIV DNA. Cereb Cortex 22(9):2065–2075

    Article  PubMed  Google Scholar 

  • Kellogg SH, McHugh PF, Bell K (2003) The Kreek-McHugh-Schluger-Kellogg scale: a new, rapid method for quantifying substance abuse and its possible applications. Drug Alcohol Depend 69(2):137–150

    Article  PubMed  Google Scholar 

  • Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD (1989) The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 46(10):1121–1123

    Article  CAS  PubMed  Google Scholar 

  • Letendre SL, Cherner M, Ellis RJ (2005) The effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease. AIDS 19(Suppl 3):S72–78

    Article  CAS  PubMed  Google Scholar 

  • Li R, Mi H, Zhao J, Yuan D, Ding J, Li H (2014) White matter damage and effects of nadir CD4+ count on patients with asymptomatic HIV associated dementia complex–a DTI study. Radiology of Infectious Diseases 1(1):11–16

    Article  Google Scholar 

  • Martin EM, Novak RM, Fendrich M et al (2004) Stroop performance in drug users classified by HIV and hepatitis C virus serostatus. J Int Neuropsychol Soc 10(2):298–300. doi:10.1017/S135561770410218XS135561770410218X

    Article  PubMed  Google Scholar 

  • Masters, M. C., & Ances, B. M. (2014, February). Role of neuroimaging in HIV associated neurocognitive disorders (HAND). In Seminars in neurology (Vol. 34, No. 1, p. 89). NIH Public Access

  • McArthur J, Smith B (2013) Neurologic complications and considerations in HIV-infected persons. Current infectious disease reports 15(1):61–66

    Article  PubMed  PubMed Central  Google Scholar 

  • McAndrews MP, Farcnik K, Carlen P et al (2005) Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology 41(4):801–808. doi:10.1002/hep.20635

    Article  PubMed  Google Scholar 

  • Murray J, Fishman SL, Ryan E et al (2008) Clinicopathologic correlates of hepatitis C virus in brain: a pilot study. J of neuroviro 14(1):17–27

    Article  CAS  Google Scholar 

  • Müller-Oehring EM, Schulte T, Rosenbloom MJ et al (2010) Callosal degradation in HIV-1 infection predicts hierarchical perception, a DTI study. Neuropsychologia 48(4):1133–1143

    Article  PubMed  Google Scholar 

  • Niciu MJ, Mason GF (2014) Neuroimaging in alcohol and drug dependence. Current behavioral neuroscience reports 1(1):45–54

    Article  PubMed  PubMed Central  Google Scholar 

  • Norman MA, Moore DJ, Taylor M et al (2011) Demographically corrected norms for African Americans and Caucasians on the Hopkins verbal learning test–revised, brief visuospatial memory test–revised, Stroop color and word test, and Wisconsin card sorting test 64-card version. J Clin Exp Neuropsychol 33(7):793–804

    Article  PubMed  PubMed Central  Google Scholar 

  • Paul RH, Letendre S, Dearborn J (2007) Cognitive function in patients co-infected with hepatitis C and human immunodeficiency virus. Current Hepatitis Reports 6:145–152

    Article  Google Scholar 

  • Pfefferbaum A, Rosenbloom MJ, Adalsteinsson E, Sullivan EV (2007) Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: synergistic white matter damage. Brain 130(1):48–64

    Article  PubMed  Google Scholar 

  • Perry W, Carlson MD, Barakat F (2005) Neuropsychological test performance in patients co-infected with hepatitis C virus and HIV. AIDS 19(Suppl 3):S79–84

    Article  PubMed  Google Scholar 

  • Radloff LS (1977) The CES-D scale a self-report depression scale for research in the general population. Applied psychological measurement 1(3):385–401

    Article  Google Scholar 

  • Ragin AB, Storey P, Cohen BA et al (2004) Whole brain diffusion tensor imaging in HIV-associated cognitive impairment. AJNR Am J Neuroradiol 25(2):195–200

    PubMed  PubMed Central  Google Scholar 

  • Ragin AB, Wu Y, Storey P et al (2005) Diffusion tensor imaging of subcortical brain injury in patients infected with human immunodeficiency virus. J Neurovirol 11(3):292–298. doi:10.1080/13550280590953799

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosas HD, Lee SY, Bender AC et al (2010) Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical “disconnection”. Neuroimage 49(4):2995–3004

    Article  PubMed  Google Scholar 

  • Shaheen AA, Myers RP (2007) Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C-related fibrosis: a systematic review. Hepatology 46(3):912–921. doi:10.1002/hep.21835

    Article  PubMed  Google Scholar 

  • Shimony JS, Epstein AA, Kroenke CD et al (2006) Diffusion modeling using Bayesian probability theory applied to imaging of multiple sclerosis. In Proc Intl Soc Mag Reson Med 14:2114

    Google Scholar 

  • Shimony JS, Sheline YI, D'Angelo G (2009) Diffuse microstructural abnormalities of normal-appearing white matter in late life depression: a diffusion tensor imaging study. Biol Psychiatry 66:45–252

    Article  Google Scholar 

  • Smith CA, Stebbins GT, Bartt RE et al (2008) Gender effects on HIV-associated white matter alterations: a voxel-wise DTI study. Brain Imaging Behav 2(3):177–191

    Article  Google Scholar 

  • Song SK, Sun SW, Ramsbottom MJ, Chang C, Russell J, Cross AH (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17(3):1429–1436.

  • Spitzer RL, Williams JBW, Gibbon M, First MB (1987) Structured Clinical Interview for DSM-III-R (SCID). New York, New York State Psychiatric Institute. Biometrics Research, 11

  • Stebbins GT, Smith A, Bartt A (2007) HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study. J Acquir Immune Defic Syndr 46(5):564–573

    Article  PubMed  Google Scholar 

  • Tate DF, Conley J, Paul RH et al (2010) Quantitative Diffusion tensor imaging tractography metrics are associated with cognitive performance among HIV-infected patients. Brain Imaging Behav 4(1):68–79

    Article  PubMed  PubMed Central  Google Scholar 

  • Thames, A. D. (2011). Past stimulant abuse is associated with reduced basal ganglia and hippocampal integrity in older HIV+ adults: a diffusion tensor imaging study. Journal of AIDS & Clinical Research

  • Thurnher MM, Castillo M, Stadler A (2005) Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients. AJNR Am J Neuroradiol 26(9):2275–281

    PubMed  Google Scholar 

  • Togwood K, Pitkanen M, Kulasegaram R (2012) Mapping the brain in younger and older asymptomatic HIV-1 men: frontal volume changes in the absence of other cortical or diffusion tensor abnormalities. Cortex 48:230–241. doi:10.1016/j.cortex.2011.03.006

    Article  Google Scholar 

  • Tural C, Tor J, Sanvisens A et al (2009) Accuracy of simple biochemical tests in identifying liver fibrosis in patients co-infected with human immunodeficiency virus and hepatitis C virus. Clin Gastroenterol Hepatol 7(3):339–345. doi:10.1016/j.cgh.2008.11.019

    Article  CAS  PubMed  Google Scholar 

  • Vargas HE, Laskus T, Radkowski M et al (2002) Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation. Liver Transpl 8(11):1014–1019

    Article  PubMed  Google Scholar 

  • von Giesen HJ, Heintges T, Abbasi-Boroudjeni N et al (2004) Psychomotor slowing in hepatitis C and HIV infection. J Acquir Immune Defic Syndr 35(2):131–137

    Article  Google Scholar 

  • Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I Conceptual framework and item selection Med Care 30(6):473–483

    PubMed  Google Scholar 

  • Wu Y, Storey P, Cohen BA et al (2006) Diffusion alterations in corpus callosum of patients with HIV. AJNR Am J Neuroradiol 27(3):656–660

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wright PW, Heaps JM, Shimony JS et al (2012) The effects of HIV and combination antiretroviral therapy on white matter integrity. AIDS 26(12):1501–1508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wright PW, Vaida FF, Fernández RJ, Rutlin J, Price RW, Lee E, Peterson J, Fuchs D, Shimony JS, Robertson KR, Walter R, Meyerhoff DJ, Spudich S, Ances BM (2015). Cerebral white matter integrity during primary HIV infection. AIDS, 29(4), 433–442

  • Zhang XD, Zhang LJ, Wu SY, Lu GM (2014) Multimodality magnetic resonance imaging in hepatic encephalopathy: an update. World journal of gastroenterology: WJG 20(32):11262

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Missouri Institute of Mental Health, University of Missouri-St. Louis, 4633 World Parkway St. Louis, St. Louis, MO, 63134, USA

    J. M. Heaps-Woodruff & R. H. Paul

  2. Department of Neurology, Washington University School of Medicine, St. Louis, USA

    P. W. Wright, B. M. Ances & D. Clifford

  3. Department of Radiology, Washington University School of Medicine, St. Louis, USA

    B. M. Ances

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  1. J. M. Heaps-Woodruff
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Correspondence to J. M. Heaps-Woodruff.

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The WUSTL Human Research Protection Office approved this study. All participants provided informed consent for this study.

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Heaps-Woodruff, J.M., Wright, P.W., Ances, B.M. et al. The impact of human immune deficiency virus and hepatitis C coinfection on white matter microstructural integrity. J. Neurovirol. 22, 389–399 (2016). https://doi.org/10.1007/s13365-015-0409-0

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