Neuropsychiatric Adverse Effects in Patients With Chronic Hepatitis C Treated by Direct Acting Antiviral Drugs

Study Overview
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Brief Summary
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Neuropsychiatric adverse effects of direct acting antiviral drugs, especially Sofosbuvir and Daclatasvir combination therapy (with or without ribavirin) in patients with chronic hepatitis C , genotype four (the predominant genotype in Egypt).

Detailed Description
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Treatment of hepatitis C virus, a virus infecting over one hundred seventy million worldwide, has evolved over the last two decades and moved from interferon-alpha monotherapy to pegylated interferon-alpha in combination with ribavirin therapy. Despite enhanced sustained virological response rates, psychiatric illness remains a barrier to widespread hepatitis C virus treatment uptake due to the neuropsychiatric risks associated with interferon-alpha.The next generation of hepatitis C virus therapeutic agents is direct acting antivirals that still require the use of interferon-ribavirin combination therapy. Poorly managed psychiatric illness can lead not only to treatment discontinuation,but also poor adherence to treatment and serious psychiatric sequels, such as suicide. Data on neuropsychiatric adverse effects of direct acting antivirals is limited and predominantly derived from landmark clinical trials for boceprevir and telaprevir.These first generation direct acting antivirals are currently not in use due to their multiple side effects ,the need for concomitant interferon-alpha ,and there wide drug-drug interactions. Recently the treatment of hepatitis C virus has undergone a paradigm shift with the introduction of the second generation of direct acting antivirals. This interferon-free modality has brought about exceptional cure rates with sustained virological response exceeding ninety hundred percent, with better tolerability, minimized side effects and short duration of treatment . Of the current hepatitis C virus treatment regimens, the combinations of Sofosbuvir plus daclatasvir have shown a high efficacy rate in achieving sustained virological response in genotype one patients. To the investigators' knowledge, the development of neuropsychiatric side effects with the use of these second generation direct acting antivirals in absence of interferon therapy, as well as the impact of the expected high sustained virological response to therapy on the psychiatric condition of patients with chronic hepatitis C (in absence of cirrhosis) have not been studied. Therefore, the purpose of this work is to evaluate the neuropsychiatric adverse effects of direct acting antivirals,especially Sofosbuvir and Daclatasvir combination therapy (with or without ribavirin) in patients with chronic hepatitis C, genotype four (the predominant genotype in Egypt).

Official Title
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Neuropsychiatric Adverse Effects in Patients With Chronic Hepatitis C Treated by Direct Acting Antiviral Drugs

Conditions
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Hepatitis C

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic hepatitis C only will be included. Patients who are eligible for treatment by DAAs only. Exclusion Criteria: Cirrhotic patients will be excluded based on USS, APRI score index and FIB4 index. Hepatitis B infected patients will also be excluded. Patients with current or previous history of neuropsychiatric disorders will be excluded. Failure to obtain consent.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with chronic hepatitis C treated by DAAs<br>All subjects will be given the same treatment regimen which includes Sofosbuvir 400 mg orally/24 hours (pre-breakfast) and Daclatasvir 60 mg orally/24 hours after lunch with or without ribavirin for a total period of 12 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton anxiety scale (HAM-A) in patients with chronic hepatitis C treated by DAAs |  | 12 months | 
| Hamilton depression scale (HAM-D) in patients with chronic hepatitis C treated by DAAs |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EEG in patients with chronic hepatitis C treated by DAAs |  | 12 months | 
| Visual evoked potential in patients with chronic hepatitis C treated by DAAs |  | 12 months |