G Oriolo1,2, E Egmond1,2,3, Z Mariño4, M Cavero1,2, R Navines1,2, L Zamarrenho5, R Solà6, J Pujol7, N Bargallo8, X Forns4, R Martin-Santos1,2,5. 1. Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain. 2. Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain. 3. Department of Health and Clinical Psychology, Faculty of Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain. 4. Liver Unit, Hospital Clinic, IDIBAPS, Centro Investigación Biomédica en Red de Enfermedades hepáticas y digestivas, (CIBEREHD), University of Barcelona, Barcelona, Spain. 5. Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil. 6. Liver Unit, Parc de Salut Mar, Universitat Autonoma de Barcelona, Barcelona, Spain. 7. MRI Research Unit, Department of Radiology, Hospital del Mar, CIBERSAM, Barcelona, Spain. 8. Center of Diagnostic Image (CDIC), Hospital Clinic, Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
Abstract
BACKGROUND: Chronic hepatitis C is considered a systemic disease because of extra-hepatic manifestations. Neuroimaging has been employed in hepatitis C virus-infected patients to find in vivo evidence of central nervous system alterations. AIMS: Systematic review and meta-analysis of neuroimaging research in chronic hepatitis C treatment naive patients, or patients previously treated without sustained viral response, to study structural and functional brain impact of hepatitis C. METHODS: Using PRISMA guidelines a database search was conducted from inception up until 1 May 2017 for peer-reviewed studies on structural or functional neuroimaging assessment of chronic hepatitis C patients without cirrhosis or encephalopathy, with control group. Meta-analyses were performed when possible. RESULTS: The final sample comprised 25 studies (magnetic resonance spectroscopy [N = 12], perfusion weighted imaging [N = 1], positron emission tomography [N = 3], single-photon emission computed tomography [N = 4], functional connectivity in resting state [N = 1], diffusion tensor imaging [N = 2] and structural magnetic resonance imaging [N = 2]). The whole sample was of 509 chronic hepatitis C patients, with an average age of 41.5 years old and mild liver disease. A meta-analysis of magnetic resonance spectroscopy studies showed increased levels of choline/creatine ratio (mean difference [MD] 0.12, 95% confidence interval [CI] 0.06-0.18), creatine (MD 0.85, 95% CI 0.42-1.27) and glutamate plus glutamine (MD 1.67, 95% CI 0.39-2.96) in basal ganglia and increased levels of choline/creatine ratio in centrum semiovale white matter (MD 0.13, 95% CI 0.07-0.19) in chronic hepatitis C patients compared with healthy controls. Photon emission tomography studies meta-analyses did not find significant differences in PK11195 binding potential in cortical and subcortical regions of chronic hepatitis C patients compared with controls. Correlations were observed between various neuroimaging alterations and neurocognitive impairment, fatigue and depressive symptoms in some studies. CONCLUSIONS: Patients with chronic hepatitis C exhibit cerebral metabolite alterations and structural or functional neuroimaging abnormalities, which sustain the hypothesis of hepatitis C virus involvement in brain disturbances.
BACKGROUND:Chronic hepatitis C is considered a systemic disease because of extra-hepatic manifestations. Neuroimaging has been employed in hepatitis C virus-infectedpatients to find in vivo evidence of central nervous system alterations. AIMS: Systematic review and meta-analysis of neuroimaging research in chronic hepatitis C treatment naive patients, or patients previously treated without sustained viral response, to study structural and functional brain impact of hepatitis C. METHODS: Using PRISMA guidelines a database search was conducted from inception up until 1 May 2017 for peer-reviewed studies on structural or functional neuroimaging assessment of chronic hepatitis Cpatients without cirrhosis or encephalopathy, with control group. Meta-analyses were performed when possible. RESULTS: The final sample comprised 25 studies (magnetic resonance spectroscopy [N = 12], perfusion weighted imaging [N = 1], positron emission tomography [N = 3], single-photon emission computed tomography [N = 4], functional connectivity in resting state [N = 1], diffusion tensor imaging [N = 2] and structural magnetic resonance imaging [N = 2]). The whole sample was of 509 chronic hepatitis Cpatients, with an average age of 41.5 years old and mild liver disease. A meta-analysis of magnetic resonance spectroscopy studies showed increased levels of choline/creatine ratio (mean difference [MD] 0.12, 95% confidence interval [CI] 0.06-0.18), creatine (MD 0.85, 95% CI 0.42-1.27) and glutamate plus glutamine (MD 1.67, 95% CI 0.39-2.96) in basal ganglia and increased levels of choline/creatine ratio in centrum semiovale white matter (MD 0.13, 95% CI 0.07-0.19) in chronic hepatitis Cpatients compared with healthy controls. Photon emission tomography studies meta-analyses did not find significant differences in PK11195 binding potential in cortical and subcortical regions of chronic hepatitis Cpatients compared with controls. Correlations were observed between various neuroimaging alterations and neurocognitive impairment, fatigue and depressive symptoms in some studies. CONCLUSIONS:Patients with chronic hepatitis C exhibit cerebral metabolite alterations and structural or functional neuroimaging abnormalities, which sustain the hypothesis of hepatitis C virus involvement in brain disturbances.