Reply
Authors: Arne Schäfer, Michael R. Kraus, Michael Scheurlen
Journal: Hepatology (2013)

We thank the editor for the opportunity to respond to the comments by Pablo Solís-Muñoz et al. We would like to address the mentioned concerns as follows. We agree with Solís-Muñoz et al. that interferon (IFN)-induced psychiatric effects may persist for some time even after the end of the antiviral treatment. However, this possible bias was avoided by choosing an evaluation timepoint of at least 1 year after the end of IFN therapy (6 months after a sustained response had been confirmed in the successfully treated group). In earlier extensive studies on interferon-induced depression (as an example, see Kraus et al., 20031) we were able to show that in all our patients the depression scores had returned to the pretreatment values 6 months after termination of IFN medication. Accordingly, in patients that may need concomitant antidepressant medication during their IFN therapy, this cotreatment can be stopped not later than 4 weeks after the antiviral therapy. Therefore, the timepoint for the reevaluation of cognitive performance of at least 1 year after the last dose of IFN was more than sufficient to exclude any persistence of IFN-related psychiatric side effects or sequelae that might have influenced our test results. Hence, we consider the difference in cognitive performance between sustained virological response (SVR) patients and nonresponders 1 year after the antiviral therapy as valid, and not clouded or biased by any "long-term IFN-associated depression." In addition, the suggested potential association between IFN-induced depression and IFN-induced neurocognitive decline could not be shown in a previous study by our group.2 Furthermore, Solís-Muñoz et al. criticize that the presented study was not blinded for therapy outcome until the time of the posttreatment tests. This aspect among others was dealt with in the Discussion section of our article, where we addressed methodological issues that are linked to the nature of the study: Randomization with respect to SVR was not feasible, neither was blinding the study an option, since it would have been unethical to withhold the information of their treatment outcome from the study patients. The response rate to an IFN-based antiviral hepatitis C therapy of 69% in a group of closely monitored and supported patients corresponds well with the data in patients with good adherence to therapy from other studies. The implication by Solís-Muñoz et al. that the treatment failure in nonresponders may be an indicator for a worse motivation in general, that then would have a negative impact on these patients' cognitive performance, is therefore highly speculative and not supported by data from any clinical trial on hepatitis C therapy. Additionally, it must be emphasized that in the pretreatment test performance no such difference in cognitive performance—and possibly motivation—was found between the patient groups. Arne Schäfer, Ph.D.1 Michael R. Kraus, M.D., Ph.D.1,2 Michael Scheurlen, M.D.1 1Medizinische Klinik und Poliklinik II Department of Gastroenterology University of Würzburg Würzburg, Germany 2Kreiskliniken Altötting-Burghausen Burghausen, Germany