RESUMEN
One of the most disabling symptoms of hepatitis C virus (HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction (PCR)-positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV-exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health-related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty-nine anti-HCV-positive individuals without advanced liver disease answered health-related quality of life (HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co-infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age-matched healthy controls. Eighty-five per cent of the patients had chronic fatigue, 50-60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue (P<.001), while cognitive deficits-especially memory function-were independent from fatigue and depression. HCV infection may cause long-standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus.
Asunto(s)
Antivirales/uso terapéutico , Fatiga/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Trastornos Mentales/epidemiología , Respuesta Virológica Sostenida , Adulto , Anciano , Estudios de Cohortes , Femenino , Hepatitis C Crónica/psicología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) infection may induce chronic fatigue and cognitive dysfunction. Virus replication was proven within the brain and HCV-positive cells were identified as microglia and astrocytes. We hypothesized that cerebral dysfunction in HCV-afflicted patients is associated with microglia activation. Microglia activation was assessed in vivo in 22 patients with chronic HCV infection compared to six healthy controls using [(11) C]-PK11195 Positron Emission Tomography (PET) combined with magnetic resonance tomography for anatomical localization. Patients were subdivided with regard to their PCR status, Fatigue Impact Scale score (FIS) and attention test sum score (ATS). A total of 12 patients (54.5%) were HCV PCR positive [of which 7 (58.3%) had an abnormal FIS and 7 (58.3%) an abnormal ATS], 10 patients (45.5%) were HCV PCR negative (5 (50%) each with an abnormal FIS or ATS). Patients without attention deficits showed a significantly higher accumulation of [(11) C]-PK11195 in the putamen (P = 0.05), caudate nucleus (P = 0.03) and thalamus (P = 0.04) compared to controls. Patients with and without fatigue did not differ significantly with regard to their specific tracer binding in positron emission tomography. Preserved cognitive function was associated with significantly increased microglia activation with predominance in the basal ganglia. This indicates a probably neuroprotective effect of microglia activation in HCV-infected patients.
Asunto(s)
Disfunción Cognitiva , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Microglía/inmunología , Adulto , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía de Emisión de PositronesRESUMEN
Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.
Asunto(s)
Apolipoproteína E4/deficiencia , Disfunción Cognitiva/psicología , Encefalopatía Hepática/psicología , Hepatitis C Crónica/patología , Memoria a Corto Plazo/fisiología , Trastornos del Humor/psicología , Enfermedades Neurodegenerativas/psicología , Adulto , Anciano , Alelos , Apolipoproteína E4/genética , Cognición , Disfunción Cognitiva/virología , Femenino , Frecuencia de los Genes/genética , Hepacivirus/genética , Encefalopatía Hepática/virología , Hepatitis C Crónica/virología , Humanos , Hígado/patología , Hígado/virología , Masculino , Persona de Mediana Edad , Trastornos del Humor/virología , Enfermedades Neurodegenerativas/virología , Pruebas Neuropsicológicas , Calidad de Vida/psicología , Encuestas y CuestionariosAsunto(s)
Trastornos del Conocimiento/diagnóstico , Infecciones por VIH/complicaciones , Hepatitis C Crónica/fisiopatología , Fármacos Anti-VIH/uso terapéutico , Cognición/fisiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Función Ejecutiva/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , Hepacivirus/fisiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Pruebas Neuropsicológicas , ARN Viral/análisis , Replicación ViralRESUMEN
Neurocognitive impairment (NCI) remains prevalent in HIV-infected subjects despite effective combination antiretroviral therapy (CART). In subjects without evidence of hepatic decompensation, NCI is also a feature of chronic HCV infection. The present study aimed to examine cerebral function and establish differences between HIV-HCV co-infected (HCVco) and HIV mono-infected (HIVmo) individuals. Neurologically asymptomatic subjects with chronic HCVco were eligible and underwent computerized neurocognitive testing (CogState; CogState Ltd, Melbourne, Australia), a dementia assessment [International HIV Dementia Scale (IHDS)] and memory assessment [the Prospective and Retrospective Memory Questionnaire (PRMQ)]. Historic control data were available for 45 HIVmo individuals and differences between study groups were assessed. Twenty-seven HCVco subjects were recruited. Plasma HIV RNA was <50 copies/mL in 25/27 of HCVco subjects and all HIVmo subjects and nadir CD4+ cell count (mean ± SD) was 214 ± 166 cells/µL and 180 ± 130 cells/µL, in HCVco and HIVmo subjects, respectively. No statistically significant differences in neurocognitive parameters or PRMQ scores were observed between groups. However, a trend towards poorer executive function score was observed in HCVco subjects (p 0.106). IHDS score (mean ± SD) was poorer in HCVco subjects (10.48 ± 1.25) vs. HIVmo subjects (11.51 ± 0.76), (p <0.001). In a multivariate model, increasing age and HCVco were the only factors significantly associated with poorer IHDS scores (p 0.039 and <0.001, respectively). In HIV-infected subjects stable on CART, statistically significantly poorer performance in the IHDS score was observed in subjects with HCVco, although no differences were observed after neurocognitive testing or memory assessment.