Long-Term Evaluation Follow-up of Neurocognitive Performance and Emotional State in Patients With Chronic Hepatitis C
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Study type: Observational

Summary: 
      This is a long-term evaluation follow-up study of neurocognitive performance and emotional
      state in patients with chronic hepatitis C infection and a former (peg)interferon
      alfa-2b-based therapy.

      M.R. Kraus, G. Teuber, NN, NN (MPsych), M. Scheurlen

      Questions:

        -  Neurocognitive and psychiatric changes induced by interferon alfa-2b therapy in patients
           with chronic hepatitis C - are they fully reversible in long-term follow-up after the
           end of antiviral treatment?

        -  At least 12 months after the end of antiviral treatment - are neurocognitive and
           mood-related parameters even significantly improved as compared to pretreatment values?
           Is this possibly only true of patients with successful virus eradication?

        -  At least 12 months after the end of antiviral treatment, is there a significant
           difference between patients with and without sustained virological response with respect
           to neurocognitive performance, emotional state and quality of life?

        -  In the absence of 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?

        -  Does the study data support an additional indication for antiviral therapy in chronic
           hepatitis C? In the case of successful virus eradication, emotional state and - above
           all - is neurocognitive performance significantly improved even in the absence of severe
           liver damage?
    

Detailed description: 
      This is a long-term evaluation follow-up study of neurocognitive performance and emotional
      state in patients with chronic hepatitis C infection and a former (peg)interferon
      alfa-2b-based therapy.

      M.R. Kraus, G. Teuber, NN, NN (MPsych), M. Scheurlen

      Questions:

        -  Neurocognitive and psychiatric changes induced by interferon alfa-2b therapy in patients
           with chronic hepatitis C - are they fully reversible in long-term follow-up after the
           end of antiviral treatment?

        -  At least 12 months after the end of antiviral treatment - are neurocognitive and
           mood-related parameters even significantly improved as compared to pretreatment values?
           Is this possibly only true of patients with successful virus eradication?

        -  At least 12 months after the end of antiviral treatment, is there a significant
           difference between patients with and without sustained virological response with respect
           to neurocognitive performance, emotional state and quality of life?

        -  Can the results of the current and previous studies be confirmed by alternative /
           additional psychometric instruments in specified subsample? (Fatigue Impact Scale;
           FIS-D, SF-36)

        -  In the absence of 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?

        -  Does the study data support an additional indication for antiviral therapy in chronic
           hepatitis C? In the case of successful virus eradication, is emotional state and - above
           all - neurocognitive performance significantly improved even in the absence of severe
           liver damage?

      Methods:

        -  Multifactorial analysis of test results: pre- vs. post-therapy; sustained virological
           response vs. nonresponse/relapse.

        -  Psychometric evaluation instruments / psychometric questionnaires (HADS-D, SCL-90-R,
           Subsample : SF-36, FIS-D)

        -  Evaluation of neurocognitive performance by the Test battery of Attentional Performance
           (TAP)

        -  Evaluation in a prospective, longitudinal study design.

      Planned sample size / sample size considerations

        -  N = 150 patients (hepatitis C patients in a longitudinal study design: t1[before onset
           of interferon therapy] … t5[at least 12 months after the end of antiviral treatment]

      Power calculations / power considerations:

        -  Given: 2-factorial design (time course x SVR); type I error = 0.050; type II error =
           0.20 (power = 0.80) - as usually assumed in clinical trials.

        -  With respect to the independent factor SVR ("sustained virological response", 2 factor
           levels), optimum / optimal sample sizes range from 42 (large effect size d = 0.8) to 102
           (medium effect size d = 0.5). Smaller effect sizes - according to previous work in this
           field - do not appear to bear any clinical relevance.

        -  (Pairwise comparisons of dependent samples [e.g. pre- vs. post-therapy or pre-therapy
           vs. long-term follow-up] require even smaller optimal sample sizes ranging from 16 to 43
           for large or medium effect sizes.)

      Patient recruitment:

        -  Patients with chronic hepatitis C infection and therapy with (peg)interferon alfa-2b.

        -  Patients with informed written consent (with respect) to a long-term follow-up of
           psychiatric side effects and neurocognitive performance.

        -  Patients with baseline monitoring of neuropsychiatric symptoms and neurocognitive
           performance.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        HCV outpatients (University Hospital)
      
Keywords: C06.552.380.705.440