Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)

Study Overview
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Brief Summary
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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.

Official Title
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Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy

Conditions
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Hepatitis C, Chronic, Cognition Disorders, Fatigue Syndrome, Chronic, Major Depressive Disorder

Intervention / Treatment
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* Drug: Interferon and ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HCV infection with genotype 1, 2, 3 or 4. Age > 18 and <60 Liver biopsy or fibroscan performed within last 5 years Signed informed consent form. Exclusion Criteria: Liver biopsy showing liver pathology not due to HCV infection. Liver cirrhosis or severe liver fibrosis Former antiviral HCV treatment (for included HCV patients). HIV and/or Hepatitis B virus infection. Alcohol or drug abuse within the last 2 years. Neutropenia, anemia or thrombocytopenia. Clinical signs of non-compensated liver pathology. Moderate to severe cardiopulmonary disease (NYHA score 1 or above) Creatinine clearance < 80mL/min. Pregnancy. Ferromagnetic implants Significant somatic disease affecting the central nervous system (somatic/neurologic disease) Head trauma resulting in unconsciousness > 5min Schizophrenia or other psychotic disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic hepatitis C treatment<br>30 Chronic HCV patients with pending antiviral treatment. A majority will have pending treatment with interferon and ribavirin, and the treated patients will be assessed 8-12 weeks after starting treatment for interferon-induced depression. | Drug: Interferon and ribavirin<br>* Interferon 180 microgram weekly s.c. and ribavirin (800/100/1200 mg daily) p.o.<br>* Other names: Pegasys (ATC Code: L03AB11) and Copegus (ATC Code: J05AB04);|
| No Intervention: Healthy Controls<br>50 age, sex and education matched controls (matched 1:1 to participants in the HCV patient groups (+/- treatment) | |
| No Intervention: Former HCV infected<br>20 Subjects with prior HCV infection identified through positive HCV antibodies, but negative HCV RNA. | |
| No Intervention: Chronic HCV patient - no treatment<br>20 chronic HCV patients without pending antiviral treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological test results, cytokine profile and MRI findings | Assessment performed before starting antiviral treatment in patients with chronic hepatitis C who awaits treatment. HCV patients without pending treatment will be tested in conjunction with their outpatient controls. | 8 weeks before starting IFN+RIB therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interferon-induced depression |  | 8-12 weeks after treatment inititation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C, cognitive dysfunction, MR spectroscopy, interferon, ribavirin, sustained virologic response, major depressive disorder, MRI