The present study evaluates neurocognitive performance as well as measures of mood, quality of life, and fatigue in patients with chronic hepatitis C infection. In a prospective longitudinal study design, included patients are monitored before, during, and in the long-term follow-up of interferon-free antiviral treatment (Sofosbuvir +/-Daclatasvir +/- Ribavirin or Sofosbuvir/Ledipasvir +/- Ribavirin). Main study goals are to compare post therapy results of sustained virologic responders to corresponding pretreatment values as well as to historic interferon-treatment patients without virological response. It is expected that HCV-associated neuropsychiatric symptoms and neurocognitive impairment is - at least in part - reversible by the successful application of modern IFN-free antiviral medication.

Chronic hepatitis C is one of the most frequent infectious diseases worldwide and a major cause of chronic liver disease. At diagnosis, approximately 20 % of patients with chronic hepatitis C already have liver cirrhosis.

Therapy for hepatitis C has meanwhile reached a high level of efficacy and effectiveness: at present, about 90 % of patients treated with a combination of peginterferon alfa, ribavirin and sofosbuvir for up to 12 weeks will reach a sustained loss of hepatitis C virus.

Psychiatric side effects of interferon alfa are well known and may require dose reduction or even premature discontinuation of therapy.

As patients on interferon treatment sometimes report concentration or memory impairment that in some cases interferes considerably with their capacity to manage the requirements of everyday life, the investigators planned and intend to conduct a prospective and longitudinal study evaluating - among other parameters - neurocognitive performance before, during, and after therapy with an antiviral IFN-free therapy.

In previously performed scientific work, the investigators were able to show that interferon-based combination therapy of chronic hepatitis C may cause reversible impairment of neurocognitive performance during treatment period. Moreover, the investigators have recently demonstrated that successful IFN-based antiviral treatment (criterion: SVR, sustained virological response) leads to significant improvement of relevant aspects of attentional and neurocognitive performance. These results indicate that HCV-related neurocognitive impairment is potentially reversible.

Nevertheless, there are still open questions and important issues to be addressed in connection with this field of research, especially regarding several aspects IFN-free antiviral therapy:

Questions to be answered:

• At least 12 months after the end of successfully performed IFN-free antiviral treatment - are psychometrically assessed parameters related to patients' quality of life, fatigue, neurocognitive performance, and mood significantly improved as compared to pretreatment (i.e., baseline) values?
• At least12 months after the end of antiviral treatment, is there a significant difference between patients with and without sustained virological response (special to historical group of IFN-treated patients without a sustained virological response) with respect to neurocognitive performance, emotional state, fatigue and quality of life?
• In the absence of a clinically significant liver damage in patients with chronic hepatitis C - does the mere presence of the hepatitis C virus have any significant influence on neurocognitive or attentional performance? Is it possible to confirm the respective findings yielded in the context of former interferon-based treatment regimens?
• With the current and upcoming IFN-free treatment options - are there still any significant therapy-related changes in symptom areas such as neurocognitive performance, mood or fatigue?

Study Design:

Prospective monocentric study with a longitudinal repeated measures design including hepatitis C patients with indication for standard IFN-free antiviral therapy (sofosbuvir/daclatasvir +/- ribavirin; sofosbuvir/ledipasvir +/- ribavirin) and a long-term follow-up of quality of life, neurocognitive performance, fatigue, and emotional state. Planned sample size: n = 30 hepatitis C patients.

Inclusion Criteria:

• Patients with chronic hepatitis C and indication for interferon-free antiviral therapy.
• Written informed consent to study participation, especially to long-term follow-up monitoring of quality of life, emotional state, fatigue, and neurocognitive performance after antiviral treatment.
• Age of study participants: between 18 and 75 years.
• At study entry, all participating patients need to have documented antibodies to HCV and circulating HCV-RNA as measured by reverse-transcription polymerase chain reaction (Cobas Amplicor HCV MonitorTM test, Roche Diagnostics)

Exclusion Criteria:

• Insufficient knowledge of the German language or cognitive impairment (due* to the indispensable application of questionnaires and the TAP, test battery of attentional performance).
• Age under 18 years or over 75 years
• Coinfections such as hepatitis B virus or human immunodeficiency virus
• Severe internal diseases (e.g., cancer, ischemic heart disease, autoimmune disease)
• Major depressive disorder (according to DSM-IV criteria), psychosis, active intravenous drug use or alcohol abuse.