Arne Schäfer

University of Wuerzburg, Würzburg, Bavaria, Germany

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Publications (27)180.47 Total impact

  • Hepatology 10/2013; · 12.00 Impact Factor
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    ABSTRACT: Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alfa-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P<0.001; shared attention - optical task, P<0.001; working memory, P<0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the post-treatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to non-responders. Conclusion: Successful eradication of HCV leads to a significant improvement of relevant aspects of attentional and neurocognitive performance, indicating that the neurocognitive impairment caused by chronic HCV infection is potentially reversible. This therefore suggests an added therapeutic benefit of antiviral treatment in HCV infection. Improvement of neurocognitive function may be an additional treatment indication in patients with HCV. (HEPATOLOGY 2013.).
    Hepatology 01/2013; · 12.00 Impact Factor
  • A Schäfer, M Scheurlen, M R Kraus
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    ABSTRACT: The efficacy of antiviral therapy in patients with chronic hepatitis C virus (HCV) infection has largely improved over the last years. Rates of long-term therapy success (sustained virological response, SVR) clearly exceed 50 % in the population of all antivirally treated HCV patients, even when including the less favourable virus genotypes 1 and 4. From recent research, it is well-known that adherence to current standard combination therapy (peginterferon alfa plus ribavirin) is crucial for the achievement of sustained response. Psychiatric adverse events, however, are subjectively very burdening and are among the most frequent reasons for premature discontinuation of antiviral therapy in HCV patients and therefore endanger therapy success. Therefore, effective side effect management regarding this branch of symptoms (e. g. depression, anger-hostility, anxiety) is to be considered crucial for the achievement of SVR. This review presents a current overview of the most relevant IFN-associated psychiatric side effects in antivirally treated patients with chronic hepatitis C infection. Moreover, various strategies for the management of these undesired conditions are reported: In particular, we address the issues of diagnostics and pretherapeutic screening for risk factors for the subsequent development of IFN-associated psychiatric symptoms. Moreover, we provide an overview of suitable instruments for the psychiatric monitoring of patients on antiviral therapy. We further discuss appropriate treatment strategies (e. g. prophylactic medication vs. medication only after the occurrence of symptoms) as well as indications for immediate therapy discontinuation due to serious psychiatric adverse events. In many cases, premature therapy discontinuation can be prevented by individual and adequate side effect management, provided that it is started in a timely manner. The continuing clinical relevance of psychiatric side effect management in this context is further backed up by the fact that also novel treatment strategies comprising protease or polymerase inhibitors will still include pegylated interferon alfa and ribavirin.
    Zeitschrift für Gastroenterologie 10/2012; 50(10):1108-13. · 1.41 Impact Factor
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    ABSTRACT: The objective of this study is to evaluate the vaccination status in rheumatoid arthritis (RA) patients during routine clinical practice, data from a German non-interventional cross-sectional study. In this prospective study, patients with rheumatoid arthritis were interviewed using a standardized questionnaire focusing on vaccination. Available vaccination documents were evaluated, and titers for common vaccination antigens (hepatitis B, rubella, mumps, measles, diphtheria, tetanus) were analyzed with special regard to the underlying treatment and age of patients. A total of 301 RA patients treated with conventional DMARDs alone (cohort I, n = 125), TNF-blocking agents (cohort II, n = 117), or B-cell depletion with rituximab (cohort III, n = 59) have been studied. Significantly more patients in the biologic cohorts II and III were aware of an increased risk of infections (I: 67.7%, II: 83.8%*, III: 89.9%*, P < 0.05). Pneumococcal vaccination rate was significantly higher (I: 20.2%, II 36.8%* and III: 39.0%*, P < 0.05) compared with cohort I. Differences were less evident for influenza. Significantly more patients ≥60 years of age have been vaccinated against Streptococcus pneumoniae and influenza. An obvious discrepancy existed between vaccination awareness and actual vaccination rates for all cohorts. No significant differences in vaccination titers could be seen between the three cohorts. Awareness of infectious complications was more present in patients treated with biologicals, and also, the rate of patients vaccinated against Streptococcus pneumoniae increased significantly depending on the underlying treatment. Nevertheless, there was a discrepancy between vaccination awareness and actual vaccination rates for all cohorts.
    Rheumatology International 02/2011; 32(6):1533-9. · 2.21 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
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    ABSTRACT: Interferon-associated depression is a frequent side effect of antiviral therapy for chronic hepatitis C. The aim of the present study was to investigate the correlation between platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations and IFN-induced depression. The study represents a secondary analysis of a previously published trial on the efficacy of SSRI medication in HCV patients on IFN therapy. Ninety-three patients were longitudinally assessed for depression and platelet serotonin. Evaluation time points were: prior to IFN therapy, at weeks 4, 12, and 24 of IFN treatment, and 4 weeks after antiviral treatment. Depression was assessed using the Hospital Anxiety and Depression Scale (HADS). Platelet serotonin concentrations were measured by ELISA. Platelet serotonin concentrations were significantly decreased during interferon therapy (p=0.001) in 74 of the 93 patients (79.6%). Clinically relevant depression occurred in 33.3% of patients - however, IFN-induced depression was not significantly linked to either baseline 5-HT concentrations or kinetics. In the subgroup of patients with IFN-induced depression who received the selective serotonin reuptake inhibitor (SSRI) citalopram (20 mg daily, n=17), serotonin levels declined further during anti-depressant medication, becoming statistically significant within the first 2 weeks (p<0.001) of SSRI treatment. We demonstrate a significant impact of IFN and SSRI intake on platelet serotonin levels, suggesting a biochemical analogy between 5-HT metabolism in blood platelets and the CNS. Platelet 5-HT levels might serve as a surrogate marker for patient adherence to antiviral and anti-depressant medication. For the prediction of IFN-induced depression, however, platelet 5-HT measurements are not suitable.
    Journal of Hepatology 10/2009; 52(1):10-5. · 9.86 Impact Factor
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    ABSTRACT: To examine among maintenance patients (methadone or buprenorphine) with and without hepatitis C virus (HCV) infection (i) the frequency of psychopathological symptoms at baseline and 1-year follow-up; (ii) the association between antiviral interferon (IFN) treatment and psychopathological symptoms; and (iii) to explore whether IFN therapy has an effect on 1-year outcome of maintenance treatment. Naturalistic prospective longitudinal cohort design. A total of 223 substitution centres in Germany. A nationally representative sample of 2414 maintenance patients, namely 800 without and 1614 with HCV infection, of whom 122 received IFN therapy. HCV infection (HCV+/HCV-), IFN (IFN+/IFN-) treatment status and clinical measures. Diagnostic status and severity (rated by clinician), psychopathology (BSI--Brief Symptom Inventory) and quality of life (EQ-5D--EuroQol Group questionnaire). HCV+ patients revealed indications for a moderately increased psychopathological burden and poorer quality of life at baseline and follow-up compared to HCV- patients. HCV+ patients showed a marked deterioration over time only in the BSI subscale somatization (P = 0.002), and the frequency of sleep disorders almost doubled over time (12.8% at baseline; 24.1% at follow-up; P < 0.01). IFN treatment, received by 10% of HCV+ patients, did not impair efficacy or tolerability of maintenance therapy and was associated overall with neither increased psychopathological burden nor reduced quality of life. Findings suggest no increased risk among HCV+ patients on maintenance therapy for depressive or other psychopathological syndromes. In our patient sample, IFN treatment was not associated with increased psychopathological burden, reduced quality of life or poorer tolerability and efficacy of maintenance treatment.
    Addiction 05/2009; 104(4):630-40. · 4.58 Impact Factor
  • M R Kraus, A Schäfer, M Scheurlen
    Gut 01/2009; 58(1):145-6. · 10.73 Impact Factor
  • A Schäfer, M Scheurlen, C Keicher, Kraus
    Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2009; 47(10).
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    ABSTRACT: Health-related quality of life (HRQoL) is impaired in patients with chronic hepatitis C. We investigated HRQoL and fatigue in patients with chronic hepatitis C virus (HCV) infection in relation to the degree of fibrosis and inflammation, and controlled for the influence of relevant demographic and medical variables. We conducted a cross-sectional two-center study including 215 outpatients with chronic hepatitis C applying the Short-Form Health Survey (SF-36) and the Fatigue Impact Scale (FIS-D). The contribution to the variability of these psychometric scores was evaluated for the degree of fibrosis as well as viremia, gender, age, mode of transmission, genotype, and ALT. There was a strong negative association between the degree of liver fibrosis and the physical SF-36 summary score (p=0.016). This was independent of the covariate age, also significantly predicting physical HRQoL (p=0.001). The absolute FIS score was significantly increased in patients with advanced fibrosis (p=0.043). In females, mental SF-36 summary score (p=0.007) and fatigue (p=0.017) were significantly more impaired. Our study suggests a significant association of physical aspects of HRQoL and fatigue with the extent of fibrosis. Fibrosis stage should be considered for the identification and management of HCV patients at risk for reduced physical HRQoL.
    Journal of Hepatology 10/2008; 49(6):923-9. · 9.86 Impact Factor
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    ABSTRACT: Interferon-induced depression represents a major complication in antiviral treatment of chronic hepatitis C virus (HCV) infection. To evaluate in a placebo-controlled study the efficacy of a selective serotonin reuptake inhibitor (SSRI) in HCV patients on antiviral therapy with interferon-associated depression. 100 HCV outpatients were included in a randomised, double-blind, placebo-controlled study. During interferon therapy (peginterferon alpha-2b plus ribavirin), depression was monitored using the Hospital Anxiety and Depression Scale (HADS). Patients with clinically relevant interferon-induced depression (HADS >or=9) were randomly assigned to placebo or citalopram (SSRI, 20 mg/day). In 28 patients (28%), HADS scores increased to >8 during interferon therapy. They were treated with placebo (n = 14) or SSRI (n = 14). HADS scores declined significantly in SSRI patients within four weeks of therapy (p<0.001) but not in placebo patients. This difference between subgroups was statistically significant (p = 0.032). Unblinding became necessary in five placebo patients as a result of intolerable depression. Rescue medication (20 mg citalopram) led to a significant decrease in HADS scores (p = 0.008). All citalopram patients were able to complete interferon therapy as planned. As an interim analysis showed a significant superiority of SSRI over placebo, the study was terminated prematurely. Three patients, who became depressed afterwards, were treated in an unblinded fashion with citalopram. The findings demonstrate clearly that citalopram treatment is highly effective in HCV patients on interferon therapy, when initiated after the onset of clinically relevant depressive symptoms. This suggests that a general SSRI prophylaxis is not necessary in these patients.
    Gut 05/2008; 57(4):531-6. · 10.73 Impact Factor
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    ABSTRACT: Transient B cell depletion with the monoclonal anti-CD20 antibody rituximab has shown favourable clinical responses in patients with rheumatoid arthritis (RA). Recently a characteristic regeneration pattern of B cell subpopulations has been reported. However, little is known about the impact of B-cell depletion on peripheral T cells in particular regulatory T cells. 17 patients with RA having failed anti-TNF were treated with rituximab. Four colour staining was performed using CD19, CD3, CD4, CD8, CD16, CD56, CD25, HLA-DR, HLA-G and intracellular Foxp3 at five time points spanning up to 12 months after rituximab. In addition, quantification of the soluble form of the HLA class I molecule HLA-G by ELISA has been performed. Peripheral B cell depletion lasted 6 to 9 months. The absolute number of CD3+, CD4+ and CD8+ lymphocytes showed no significant changes up to 1 year after B-cell depletion compared to before therapy. Only the relative frequency for CD3 and CD4 showed a significant increase (p < 0.05). In particular, CD4+CD25++ and Foxp3 positive regulatory T cells remained constant. The percentage of HLA-G positive cells in the CD4+ or CD8+ population did not change significantly either. The amount of sHLA-G remained without significant changes. Absolute T cell counts showed no significant changes after rituximab compared to the time point before therapy.In particular, the frequency of regulatory T cells with a CD4+CD25++ phenotype as well as positive Foxp3 expression were numerically stable. Additionally, HLA-G positive regulatory T cells and soluble levels of HLA-G showed no significant changes.
    The Open Rheumatology Journal 01/2008; 2:81-8.
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    ABSTRACT: Interferon-induced depression is a major complication in antiviral therapy of chronic hepatitis C. Little is known about underlying mechanisms and reliable predictive factors associated with cytokine-induced depressive symptoms. In a cohort of 139 hepatitis C-infected outpatients treated with interferon alfa-2b, we investigated the impact of functional gene variants of the cerebral serotonin (5-HT) signalling pathway previously implicated in depression risk. Depression was monitored using the Hospital Anxiety and Depression Scale (HADS). All patients were genotyped for functional variations in the 5-HT(1A) receptor (HTR1A), 5-HT transporter (SLC6A4, 5-HTT), and tryptophan hydoxylase-2 (TPH2). Homozygosity for the HTR1A-1019G variant significantly increased both incidence and severity of interferon-induced depression. Maximum increases in HADS depression scores during antiviral therapy correlated with HTR1A variation (P = .011). Clinically relevant depression was significantly associated with the HTR1A-1019G genotype (P = .017; OR, 2.95). 5-HTT and TPH2 variations did not contribute significantly to the prediction of interferon-induced depression by HTR1A (sensitivity, 35.9%; specificity, 84.0%). Our findings suggest an impact of allelic variation in 5-HT(1A) receptor expression on the development of interferon alfa-induced depression during antiviral treatment of chronic hepatitis C. Prediction models of interferon-induced depressive symptoms based on HTR1A variation offer a perspective for an antidepressant selective serotonin reuptake inhibitor prophylaxis in patients genetically at risk for interferon-induced depression.
    Gastroenterology 04/2007; 132(4):1279-86. · 12.82 Impact Factor
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    ABSTRACT: In recent years, research on interferon (IFN)-induced depressive symptoms in antivirally treated patients suffering from chronic hepatitis C (CHC) has considerably intensified. Profound scientific knowledge of this complication is of great relevance with regard to adherence, compliance, and premature therapy discontinuation. Presently, there is considerable variability of both, the frequency and extent of IFN-induced depression reported in different cohorts of patients. The aim of the presented study was to systematically review recent literature of research within this field; and particularly (1) to identify to what extent methodological bias contributed to inconsistent results in different studies, (2) to critically appraise methods and results of studies published so far, and (3) to suggest directions for future work, especially with respect to alternative and improved methodological approaches. The results of this critical review suggest that the variability of findings seem to be largely due to different study populations, treatment regimens, methodological approaches, and sometimes arbitrary or at least poorly defined choice of screening instruments for depression, particularly criteria for clinically relevant depression (cut-off criteria). Study designs and methodological approaches to investigate IFN-alfa-induced depression in patients with CHC have been incoherent. Future research in this field needs agreement on the use of standardized assessment of IFN-induced depression in CHC. Furthermore, objective criteria and guidelines for the treatment of IFN-induced depression in these patients are needed in clinical practice.
    International Journal of Methods in Psychiatric Research 02/2007; 16(4):186-201. · 1.76 Impact Factor
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    ABSTRACT: The study objective was to determine the contribution of cytokine-induced depression to a predictive model of sustained virological response (SVR) in chronic hepatitis C. One hundred and one therapy-naïve hepatitis C virus (HCV) outpatients received treatment with peginterferon alfa-2b and ribavirin. Neuropsychiatric side effects were monitored prospectively (Hospital Anxiety and Depression Scale, DSM-IV criteria for major depression). SVR was defined as a failure to detect HCV by PCR 24 weeks after therapy. SVR rate was 72.3% (73 of 101 patients). Classification data and the extent of interferon-induced depression were not significantly linked to SVR. Virus genotype (p = 0.045) and gender (p = 0.016) contributed significantly to a logistic regression model. Mean (p = 0.811) and maximum (p = 0.744) depression increases were no significant predictors of SVR. Major depression rates (DSM-IV criteria) were 12.3% (9 of 73 patients) in the subgroup with SVR and 10.7% (3 of 28) in patients without SVR. We found no significant association between depression and the efficacy of antiviral treatment in chronic hepatitis C. Interferon-induced depressive symptoms are important to be monitored and treated if necessary; however, they cannot be used to predict therapy success.
    Chemotherapy 02/2007; 53(4):292-9. · 2.07 Impact Factor
  • Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2007; 45(10).
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    ABSTRACT: In chronic hepatitis C infection, the doctor-patient relationship can be burdened for various reasons. Factors associated with the doctor-patient relationship and self-disclosure of hepatitis C virus (HCV) status have not so far been investigated systematically. The goal of the study was to examine self-disclosure of HCV positivity, perceived stigmatization, and potential predictor variables in a German outpatient group. In a cross-sectional single-centre study, we included a volunteer sample of 103 HCV outpatients. Patient recruitment was between March 2003 and September 2004. Data were obtained from a fully standardized face-to-face interview [HCV disclosure behaviour (main interview variable), stigmatization, doctor-patient relationship] and psychometric self-assessment questionnaires [Hospital Anxiety and Depression Scale, German version; Symptom Checklist-90 Revised (global severity index); Inventory of Interpersonal Problems (total score)]. The overall general disclosure rate was 44.7% (with respect to all physicians). However, 75% stated revealing their positive serostatus in future physician appointments (P < 0.05). With respect to family/friends, disclosure rates were clearly higher (permanent partner, 99%; average, 76.7%). Patients' disclosure behaviour could not be predicted by sociodemographic variables or personality factors (binary logistic regression, P > 0.05). Similarly, the Hospital Anxiety and Depression Scale and Symptom Checklist-90 subscales were not substantially associated with HCV disclosure. Experiences of stigmatization (rate 38.8%) were more frequent in women (P = 0.014) and patients with higher depression scores (P = 0.029). There is a need for education in the field of chronic hepatitis C in order to improve the physician-patient relationship. HCV disclosure rates might thus be increased and the frequency of problematic contacts reduced. Importantly, the data show that physicians should explicitly ask for the patients' HCV status because unrequested disclosure cannot be taken for granted.
    European Journal of Gastroenterology & Hepatology 12/2005; 17(12):1387-94. · 1.92 Impact Factor
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    ABSTRACT: Decrease of libido and erectile dysfunction are reported by male patients during antiviral therapy of chronic hepatitis C, but therapy-associated underlying factors for sexual dysfunction are not well defined. To assess putative contributions of interferon-induced sex hormone changes to sexual dysfunction, we prospectively investigated changes in free testosterone, total testosterone, dehydroepiandrosterone sulfate, prolactin, sex hormone-binding globulin, FSH and LH levels and psychometric self-assessment scores in 34 male patients treated with interferon alfa-2b (5 MIU three times weekly) (n=19)+ ribavirin (n=15) for 6-12 months. Depression was measured by the Hospital Anxiety and Depression Scale. Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a five-point rating scale assessing sexual arousal disorder. Free and total testosterone decreased significantly during antiviral therapy in close correlation with libido/sexual function. Depression scores increased during therapy and were also significantly associated with sexual dysfunction. However, androgen levels displayed no significant correlation with depression. These results suggest that interferon-induced decrease in sexual function is associated - but not causally related -with both androgen reduction and increased depressive symptoms. These findings may affect care for male hepatitis C patients during interferon therapy.
    Journal of Endocrinology 06/2005; 185(2):345-52. · 4.06 Impact Factor
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    ABSTRACT: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon. Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98 patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 mug peginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R). Therapy with pegylated interferon alfa-2b produces comparable scores for depression (ANOVA: P = 0.875) as compared to conventional interferon. Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups. Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.
    World Journal of Gastroenterology 04/2005; 11(12):1769-74. · 2.55 Impact Factor

Publication Stats

649 Citations
180.47 Total Impact Points

Institutions

  • 2001–2013
    • University of Wuerzburg
      • Department of Internal Medicine II
      Würzburg, Bavaria, Germany
  • 2009
    • Technische Universität Dresden
      Dresden, Saxony, Germany
  • 2008
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany