Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)
Status:
Completed
Trial end date:
2012-11-01
Target enrollment:
Participant gender:
Summary
Patients with HCV infection often suffer from chronic fatigue, depression and reduced
cognition, even before evolving severe liver fibrosis, liver cirrhosis and hepatic
encephalopathy.
It is currently unclear to what extent the symptoms er due to a direct pathological effects
of the virus itself, or due to pre-existing psychiatric disease. There is a complex
relationship between prior or existing drug abuse, psychiatric disease and HCV infection,
that makes it difficult to establish cause-effect relationships.
A biological mechanism has been suggested to contribute to development of cerebral
dysfunction in the patients. According to the prevailing Trojan Horses hypothesis circulating
lymphocytes cross the blood brain barrier carrying HCV to the central nervous system and
virus is subsequently replicated in the macrophages and the microglia in brain as a separate
compartment. As part of the immunological response to viral replication, neurodegenerative
processes takes place with a harmful effect on the neural circuit and cerebral function.
Identification of HCV RNA negative strand, a replication product, in brain tissue from HCV
patients, as part of autopsy studies, supports the hypothesis. Moreover, HCV patients have
also been observed with abnormal metabolic concentrations in the frontal white substance and
the basal ganglia by MRI spectroscopy compared to control groups.
The overall study objective is to assess cerebral function with particular emphasis on
cognitive functions in HCV patients (genotypes 1,2,3 and 4) by use of a neuropsychiatric test
battery. Furthermore, the patients will be examined by MRI, including magnetization transfer,
diffusion tensor and contrast perfusion, in order to perform measurements of cerebral
volumetric and microstructure. Finally, HCV analysis, including viral sequences and cytokine
profiles, in serum and cerebrospinal fluid will be carried out in the study population.