Neurocognitive Changes in Patients with Hepatitis C Receiving Interferon alfa-2b and Ribavirin*

Department of Gastroenterology and hepatology, Medizinische Poliklinik, University of Würzburg, D-97070 Würzburg, Germany.
Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.9). 12/2004; 77(1):90-100. DOI: 10.1016/j.clpt.2004.09.007

ABSTRACT Background
During antiviral therapy of chronic hepatitis C, patients frequently report impairment of concentration or memory. Therefore we prospectively investigated neurocognitive performance in patients receiving interferon alfa and ribavirin.Methods
Repeated computer-based testing of neurocognitive function was performed in 70 patients with chronic hepatitis C receiving interferon alfa-2b (pegylated or conventional) and ribavirin. In addition, depression scores were obtained (Hospital Anxiety and Depression Scale).ResultsReaction times were significantly increased during treatment (mean reaction time increase after 3 months of therapy: alertness, 46.76 ms [95% confidence interval (CI)], 26.86-66.66 ms), P < .001; divided attention, 47.04 ms [95% CI, 26.44-67.64 ms], P < .001; vigilance, 60.78 ms [95% CI, 29.24-92.32 ms], P < .001; and working memory, 38.53 ms [95% CI, 1.22-75.83], P = .34). Accuracy measures (number of false reactions) were affected for the working-memory task exclusively. Cognitive performance returned to pretreatment values after the end of therapy. Cognitive impairment was not significantly correlated with the degree of concomitant depression (0.04 < r [absolute value] < 0.10, P > .390).Conclusions
Interferon-based combination therapy of chronic hepatitis C causes significant but reversible impairment of neurocognitive performance. Consequences for the requirements of an active life in patients with chronic hepatitis C receiving antiviral therapy need to be assessed.Clinical Pharmacology & Therapeutics (2005) 77, 90-100; doi: 10.1016/j.clpt.2004.09.007

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    • "Furthermore, there is evidence that HCV infection impacts decision-making as measured by delay discounting, or consistent selection of smaller immediate rewards rather than larger delayed awards, which is suggestive of increased impulsivity (Huckans et al., 2011). It is not clear whether the neurocognitive effects of HCV are reversible following treatment and viral clearance (e.g., Kraus et al., 2005), or whether there are lasting effects (e.g., Patullo, McAndrews, Damyanovich, & Heathcote, 2011). "
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    ABSTRACT: Approximately one-third of persons infected with the hepatitis C virus (HCV) evidence mild cognitive impairment that is consistent with frontostriatal systems dysfunction, including cognitive dyscontrol, and impacts everyday functioning. The present study examined the effects of HCV on neurocognitive dispersion, or within-person variability in neurocognitive performance across domains, which may be a function of poor sustained cognitive control. High dispersion was also hypothesized to increase risk for unemployment. The study sample included 37 individuals with HCV infection (HCV+) and 45 demographically comparable uninfected comparison participants (HCV-). Dispersion was operationalized as an intra-individual standard deviation (ISD) calculated across the demographically adjusted T-scores of 13 standard neuropsychological tests. Multiple linear regression and logistic regression approaches were used to evaluate associations between dispersion and HCV serostatus and employment status, respectively. HCV serostatus was significantly associated with higher dispersion, independent of mean level of neurocognitive ability, psychiatric factors, and liver disease severity. Within the HCV+ group, higher dispersion was associated with an increased risk of unemployment among individuals with higher overall mean neurocognitive ability. Increased neurocognitive dispersion among HCV+ individuals may indicate vulnerability to cognitive dyscontrol expressed as poor regulation of performance across tasks. Higher dispersion may manifest as functional difficulties in daily life, particularly among neurocognitively normal HCV-infected persons, which speaks to the potential clinical value of considering intra-individual variability when evaluating risk for everyday function problems in this population.
    The Clinical Neuropsychologist 04/2012; 26(4):654-74. DOI:10.1080/13854046.2012.680912 · 1.72 Impact Factor
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    • "The purpose of the control sample was twofold: to control for the variability of cerebral metabolites in HCV positive patients over time, and to control for the practice effect of repeat neuropsychological testing at an interval of 12 weeks. While the cognitive effects of interferon are reportedly reversed within 4–6 weeks of stopping treatment, [17] the effect of interferon on cerebral metabolites is unknown and as such an interferon 'wash-out' period of 2 years was required for eligibility in subjects previously treated with interferon alfa. "
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    ABSTRACT: Chronic hepatitis C virus (HCV) infection is associated with altered cerebral metabolism and cognitive dysfunction. We aimed to evaluate the effect of pegylated interferon/ribavirin (PIFN/R) and HCV clearance on cerebral metabolism, and neuropsychological performance. Fifteen non-cirrhotic HCV positive subjects underwent (1)H MR spectroscopy (MRS) before, during, and after treatment with PIFN/R. The metabolites of interest namely, N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), and the control metabolite creatine (Cr), were acquired from 3 different brain regions; left basal ganglia, left frontal cortex, and left dorso-lateral pre-frontal cortex. Coinciding with this, subjects also underwent a battery of neuropsychological tests to evaluate the domains of verbal learning, memory, attention, language, executive functioning, and motor skills. Seven HCV positive controls (not receiving anti-viral therapy) underwent MRS and neuropsychological testing at two time points, 12 weeks apart, to examine for variation in cerebral metabolites over time and the practice effect of repeat neuropsychological testing. Significant reductions in basal ganglia Cho/Cr (p=0.03) and basal ganglia MI/Cr (p=0.03) were observed in sustained virological responders (SVRs, n=8), but not non-responders/relapsers (NR/R, n=6), indicative of reduced cerebral infection and/or immune activation in those who cleared virus. SVRs demonstrated significant improvements in verbal learning, memory, and visuo-spatial memory. A small but significant improvement in neurocognitive function secondary to the practice effect was seen in both HCV controls and HCV subjects during treatment. HCV eradication has a beneficial effect on cerebral metabolism and selective aspects of neurocognitive function and is an important factor when contemplating anti-viral therapy in HCV, especially in those with mild disease.
    Journal of Hepatology 03/2012; 56(3):549-56. DOI:10.1016/j.jhep.2011.09.015 · 11.34 Impact Factor
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    • "Debien and colleagues (2001) showed that more than 30% of patients treated by IFN- presented various psychiatric disorders including depression, anxiety, intense and fluctuating personality disorders, manic or psychotic symptoms, and suicidal tendencies. Others have described declines in concentration, attention, memory and episodic dizzy spells and headaches (Kraus et al., 2005). Yet, the target cells of systemic IFN-treatment on the neurological and psychiatric effects remain undefined. "
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    NeuroToxicology 03/2009; 30(2-30):261-268. DOI:10.1016/j.neuro.2008.12.012 · 3.38 Impact Factor
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