Top

Published in:

01-04-2016 | Original Article

Reduced cerebral cortical thickness in Non-cirrhotic patients with hepatitis C

Authors: Simon Hjerrild, Signe Groth Renvillard, Peter Leutscher, Leif Hougaard Sørensen, Leif Østergaard, Simon Fristed Eskildsen, Poul Videbech

Published in: Metabolic Brain Disease | Issue 2/2016

Abstract

Hepatitis C virus (HCV) infection is associated with fatigue, depression, and cognitive impairment even in the absence of severe liver fibrosis or cirrhosis. HCV has been hypothesised to cause neurodegenerative changes through low-grade neuroinflammation. Our aim was to examine whether cortical thickness (CTh) differs between chronic HCV patients and healthy controls, suggestive of cortical atrophy. In this case–control study 43 HCV patients without severe liver fibrosis, substance abuse, or comorbid HIV or hepatitis B virus infection, and 43 age and sex matched controls underwent MRI. Cortical thickness was measured using a surface based approach. Participants underwent semi-structured psychiatric interview and fatigue was assessed using the fatigue severity scale. HCV was associated with higher fatigue scores, and 58 % of HCV patients suffered from significant fatigue (p < 0.0001). Depression was observed in 16 % of patients. Areas of significantly reduced CTh were found in both left and right occipital cortex and in the left frontal lobe after correction for multiple comparisons (p < 0.05). No association between fatigue, former substance abuse, or psychotropic medication and CTh was found. No overall difference in cerebral white and grey matter volume was found. The findings support the hypothesis that HCV is associated with neurodegenerative changes.

Anthony IC, Bell PJE (2008) The neuropathology of HIV/AIDS. Int Rev Psychiatry 20:15–24. doi:10.1080/09540260701862037 CrossRefPubMed

Aubert-Broche B, Fonov VS, García-Lorenzo D et al (2013) A new method for structural volume analysis of longitudinal brain MRI data and its application in studying the growth trajectories of anatomical brain structures in childhood. Neuroimage 82:393–402. doi:10.1016/j.neuroimage.2013.05.065 CrossRefPubMed

Bladowska J, Zimny A, Knysz B et al (2013) Evaluation of early cerebral metabolic, perfusion and microstructural changes in HCV-positive patients: a pilot study. J Hepatol. doi:10.1016/j.jhep.2013.05.008 PubMed

Bladowska J, Knysz B, Zimny A et al (2014) Value of perfusion-weighted MR imaging in the assessment of early cerebral alterations in neurologically asymptomatic HIV-1-positive and HCV-positive patients. PLoS One 9:e102214. doi:10.1371/journal.pone.0102214 CrossRefPubMedPubMedCentral

Bokemeyer M, Ding XQ, Goldbecker A et al (2011) Evidence for neuroinflammation and neuroprotection in HCV infection-associated encephalopathy. Gut 60:370–377. doi:10.1136/gut.2010.217976 CrossRefPubMed

Cardinale F, Chinnici G, Bramerio M et al (2014) Validation of FreeSurfer-estimated brain cortical thickness: comparison with Histologic measurements. Neuroinformatics. doi:10.1007/s12021-014-9229-2 PubMed

Chiu W-C, Tsan Y-T, Tsai SL et al (2014) Hepatitis C viral infection and the risk of dementia. Eur J Neurol 21:1068–e59. doi:10.1111/ene.12317 CrossRefPubMed

Collins DL, Evans AC (1997) ANIMAL: validation and applications of non-linear registration-based segmentation. Int J Pattern Recognit Artif Intell 11:1271–1294CrossRef

Collins DL, Neelin P, Peters TM, Evans AC (1994) Automatic 3D intersubject registration of MR volumetric data in standardized talairach space. J Comput Assist Tomogr 18:192–205CrossRefPubMed

Collins DL, Zijdenbos AP, Baare WFC, Evans AC (1999) ANIMAL + INSECT: improved cortical structure segmentation. In: Kuba A (ed) IPMI. pp 210–223

Coupe P, Yger P, Prima S et al (2008) An optimized blockwise nonlocal means denoising filter for 3-D magnetic resonance images. IEEE Trans Med Imaging 27:425–441. doi:10.1109/TMI.2007.906087 CrossRefPubMedPubMedCentral

Coupé P, Manjón JV, Gedamu E et al (2010) Robust Rician noise estimation for MR images. Med Image Anal 14:483–493. doi:10.1016/j.media.2010.03.001 CrossRefPubMed

Dittner AJ, Wessely SC, Brown RG (2004) The assessment of fatigue: a practical guide for clinicians and researchers. J Psychosom Res 56:157–170. doi:10.1016/S0022-3999(03)00371-4 CrossRefPubMed

Eskildsen SF, Østergaard LR (2006) Active surface approach for extraction of the human cerebral cortex from MRI. Med Image Comput Comput Assist Interv 9:823–830PubMed

Eskildsen SF, Østergaard LR (2007) Quantitative comparison of two cortical surface extraction methods using MRI phantoms. Med Image Comput Comput Assist Interv 10:409–416PubMed

Eskildsen SF, Østergaard LR (2008) Evaluation of five algorithms for mapping brain cortical surfaces. Computer graphics and image processing, 2008 SIBGRAPI ′08 XXI Brazilian symposium on 137–144.

Eskildsen SF, Uldahl M, Østergaard LR (2005) Extraction of the cerebral cortical boundaries from MRI for measurement of cortical thickness. In: Fitzpatrick JM, Reinhardt JM (eds) Proc. SPIE 5747, Medical Imaging 2005: Image processing. pp 1400–1410

Eskildsen SF, Coupé P, Fonov V et al (2012) BEaST: brain extraction based on nonlocal segmentation technique. Neuroimage 59:2362–2373. doi:10.1016/j.neuroimage.2011.09.012 CrossRefPubMed

Eskildsen SF, Coupé P, García-Lorenzo D et al (2013) Prediction of Alzheimer’s disease in subjects with mild cognitive impairment from the ADNI cohort using patterns of cortical thinning. Neuroimage 65C:511–521. doi:10.1016/j.neuroimage.2012.09.058 CrossRef

Fishman SL, Murray JM, Eng FJ et al (2008) Molecular and bioinformatic evidence of hepatitis C virus evolution in brain. J Infect Dis 197:597–607. doi:10.1086/526519 CrossRefPubMedPubMedCentral

Fletcher NF, McKeating JA (2012) Hepatitis C virus and the brain. J Viral Hepat 19:301–306. doi:10.1111/j.1365-2893.2012.01591.x CrossRefPubMed

Fonov V, Evans AC, Botteron K et al (2011) Unbiased average age-appropriate atlases for pediatric studies. Neuroimage 54:313–327. doi:10.1016/j.neuroimage.2010.07.033 CrossRefPubMedPubMedCentral

Forton DM, Allsop JM, Main J et al (2001) Evidence for a cerebral effect of the hepatitis C virus. Lancet 358:38–39. doi:10.1016/S0140-6736(00)05270-3 CrossRefPubMed

Forton DM, Karayiannis P, Mahmud N et al (2004) Identification of unique hepatitis C virus quasispecies in the central nervous system and comparative analysis of internal translational efficiency of brain, liver, and serum variants. J Virol 78:5170–5183CrossRefPubMedPubMedCentral

Forton DM, Hamilton G, Allsop JM et al (2008) Cerebral immune activation in chronic hepatitis C infection: a magnetic resonance spectroscopy study. J Hepatol 49:316–322. doi:10.1016/j.jhep.2008.03.022 CrossRefPubMed

Golden J, O’Dwyer AM, Conroy RM (2005) Depression and anxiety in patients with hepatitis C: prevalence, detection rates and risk factors. Gen Hosp Psychiatry 27:431–438. doi:10.1016/j.genhosppsych.2005.06.006 CrossRefPubMed

Grover VP, Pavese N, Koh SB et al (2012) Cerebral microglial activation in patients with hepatitis c: in vivo evidence of neuroinflammation. J Viral Hepat 19:e89–96. doi:10.1111/j.1365-2893.2011.01510.x CrossRefPubMed

Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62CrossRefPubMedPubMedCentral

Hassoun Z, Willems B, Deslauriers J et al (2002) Assessment of fatigue in patients with chronic hepatitis C using the fatigue impact scale. Dig Dis Sci 47:2674–2681CrossRefPubMed

Kallianpur KJ, Kirk GR, Sailasuta N et al (2012) Regional cortical thinning associated with detectable levels of HIV DNA. Cereb Cortex 22:2065–2075. doi:10.1093/cercor/bhr285 CrossRefPubMedPubMedCentral

Kleinman L, Zodet MW, Hakim Z et al (2000) Psychometric evaluation of the fatigue severity scale or use in chronic hepatitis C. Qual Life Res 9:499–508CrossRefPubMed

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 46:1121–1123CrossRefPubMed

Laskus T, Radkowski M, Adair DM et al (2005) Emerging evidence of hepatitis C virus neuroinvasion. AIDS 19(Suppl 3):S140–4CrossRefPubMed

Lerdal A, Wahl A, Rustøen T et al (2005) Fatigue in the general population: a translation and test of the psychometric properties of the Norwegian version of the fatigue severity scale. Scand J Public Health 33:123–130. doi:10.1080/14034940410028406 CrossRefPubMed

Maes M, Berk M, Goehler L et al (2012) Depression and sickness behavior are janus-faced responses to shared inflammatory pathways. BMC Med 10:66. doi:10.1186/1741-7015-10-66 CrossRefPubMedPubMedCentral

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 41:801–808. doi:10.1002/hep.20635 CrossRefPubMed

Nygaard GO, Walhovd KB, Sowa P et al (2014) Cortical thickness and surface area relate to specific symptoms in early relapsing-remitting multiple sclerosis. Mult Scler. doi:10.1177/1352458514543811 PubMed

Oster S, Christoffersen P, Gundersen HJ et al (1993) Cerebral atrophy in AIDS: a stereological study. Acta Neuropathol 85:617–622CrossRefPubMed

Pakkenberg B, Gundersen HJ (1997) Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 384:312–320CrossRefPubMed

Pelvig DP, Pakkenberg H, Stark AK, Pakkenberg B (2008) Neocortical glial cell numbers in human brains. Neurobiol Aging 29:1754–1762. doi:10.1016/j.neurobiolaging.2007.04.013 CrossRefPubMed

Perry W, Hilsabeck RC, Hassanein TI (2008) Cognitive dysfunction in chronic hepatitis C: a review. Dig Dis Sci 53:307–321. doi:10.1007/s10620-007-9896-z CrossRefPubMed

Piche T, Gelsi E, Schneider SM et al (2002) Fatigue is associated with high circulating leptin levels in chronic hepatitis C. Gut 51:434–439CrossRefPubMedPubMedCentral

Poynard T, Cacoub P, Ratziu V et al (2002) Fatigue in patients with chronic hepatitis C. J Viral Hepat 9:295–303CrossRefPubMed

Radkowski M, Wilkinson J, Nowicki M et al (2002) Search for hepatitis C virus negative-strand RNA sequences and analysis of viral sequences in the central nervous system: evidence of replication. J Virol 76:600–608CrossRefPubMedPubMedCentral

Saunders JB, Aasland OG, Babor TF et al (1993) Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II. Addiction 88:791–804CrossRefPubMed

Seaman K, Paterson BL, Vallis M et al (2009) Future directions for investigation of fatigue in chronic hepatitis C viral infection. Chronic Illness 5:115–128. doi:10.1177/1742395309104476 CrossRefPubMed

Sled JG, Zijdenbos AP, Evans AC (1998) A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 17:87–97. doi:10.1109/42.668698 CrossRefPubMed

Thompson PM, Dutton RA, Hayashi KM et al (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4 + T lymphocyte decline. Proc Natl Acad Sci U S A 102:15647–15652. doi:10.1073/pnas.0502548102 CrossRefPubMedPubMedCentral

Treadway MT, Waskom ML, Dillon DG et al (2014) Illness progression, recent stress, and morphometry of Hippocampal subfields and medial prefrontal cortex in major depression. Biol Psychiatry. doi:10.1016/j.biopsych.2014.06.018 PubMedPubMedCentral

Tucker KA, Robertson KR, Lin W et al (2004) Neuroimaging in human immunodeficiency virus infection. J Neuroimmunol 157:153–162. doi:10.1016/j.jneuroim.2004.08.036 CrossRefPubMed

Vivithanaporn P, Maingat F, Lin LT et al (2010) Hepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicity. PLoS One 5:e12856. doi:10.1371/journal.pone.0012856 CrossRefPubMedPubMedCentral

Wang L, Goldstein FC, Veledar E et al (2009) Alterations in cortical thickness and white matter integrity in mild cognitive impairment measured by whole-brain cortical thickness mapping and diffusion tensor imaging. Am J Neuroradiol 30:893–899. doi:10.3174/ajnr.A1484 CrossRefPubMedPubMedCentral

Wang X, Xie H, Cotton AS et al (2014) Early cortical thickness changes after mild traumatic brain injury following motor vehicle collision. J Neurotrauma. doi:10.1089/neu.2014.3492

Weissenborn K, Krause J, Bokemeyer M et al (2004) Hepatitis C virus infection affects the brain-evidence from psychometric studies and magnetic resonance spectroscopy. J Hepatol 41:845–851. doi:10.1016/j.jhep.2004.07.022 CrossRefPubMed

Wilkinson J, Radkowski M, Laskus T (2009) Hepatitis C virus neuroinvasion: identification of infected cells. J Virol 83:1312–1319. doi:10.1128/JVI.01890-08 CrossRefPubMedPubMedCentral

Wilkinson J, Radkowski M, Eschbacher JM, Laskus T (2010) Activation of brain macrophages/microglia cells in hepatitis C infection. Gut 59:1394–1400. doi:10.1136/gut.2009.199356 CrossRefPubMed

Wing JK, Babor T, Brugha T et al (1990) SCAN. Schedules for clinical assessment in neuropsychiatry. Arch Gen Psychiatry 47:589–593CrossRefPubMed

Wing JK, Ustun TB, Sartorius N (1998) Diagnosis and clinical measurement in psychiatry: a reference manual for SCAN. Cambridge University Press, Cambridge

Worsley KJ, Andermann M, Koulis T et al (1999) Detecting changes in nonisotropic images. Hum Brain Mapp 8:98–101CrossRefPubMed

Title: Reduced cerebral cortical thickness in Non-cirrhotic patients with hepatitis C
Authors: Simon Hjerrild
Signe Groth Renvillard
Peter Leutscher
Leif Hougaard Sørensen
Leif Østergaard
Simon Fristed Eskildsen
Poul Videbech
Publication date: 01-04-2016
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 2/2016
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-015-9752-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Reduced cerebral cortical thickness in Non-cirrhotic patients with hepatitis C

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2016

Predicted structure of MIF/CD74 and RTL1000/CD74 complexes

Chronic combined stress induces selective and long-lasting inflammatory response evoked by changes in corticosterone accumulation and signaling in rat hippocampus

Accumulation of reactivity to MBP sensitizes TRAIL mediated oligodendrocyte apoptosis in adult sub cortical white matter in a model for human multiple sclerosis

Echinocystic acid reduces reserpine-induced pain/depression dyad in mice

Cerebral malaria – clinical manifestations and pathogenesis

Effects of common chronic medical conditions on psychometric tests used to diagnose minimal hepatic encephalopathy