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Unlabelled: Treatment of chronic hepatitis C with pegylated interferon (peginterferon) and ribavirin can cause or exacerbate depression but its effects on cognitive function are largely unknown. The aim of this study was to determine whether treatment with peginterferon and ribavirin adversely impacts cognitive function in patients with chronic hepatitis C. Prior nonresponders to interferon were retreated with peginterferon alfa-2a and ribavirin for 24 (n=177) or 48 weeks (n=57) in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial. Cognitive function was prospectively assessed using a battery of 10 standardized neuropsychological tests at weeks 0, 24, 48, and 72. Cognitive impairment was defined based upon a global deficit score. The Beck Depression Inventory and Brief Symptom Inventory were used to assess mood status. The 57 subjects who completed 48 weeks of antiviral therapy reported significant increases in difficulty concentrating, emotional distress, and symptoms of depression, all of which improved after cessation of therapy [P<0.0001, analysis of variance (ANOVA)]. Nonetheless, the frequency of cognitive impairment did not increase during the first 24 weeks of treatment in 177 patients (34% versus 32%, P=0.64) nor in the 57 patients completing 48 weeks of treatment (P=0.48, ANOVA)., Conclusion: Retreatment of prior non-responders with peginterferon and ribavirin was not associated with objective evidence of cognitive impairment as measured by a comprehensive battery of neuropsychological tests. The lack of cognitive impairment is reassuring and suggests that self-reported symptoms of cognitive dysfunction are more likely related to the systemic and psychiatric side effects of antiviral treatment rather than measurable changes in cognition.

Mild neuropsychological impairment has previously been reported in chronic hepatitis C (CHC) patients. The aim of this study was to assess the presence and severity of cognitive impairment among a cohort of CHC patients with advanced fibrosis using clinician ratings compared to classification based upon statistical methods. In addition, we set out to determine the relationship between cognitive scores and functional status. Two experienced neuropsychologists provided "clinician ratings" on a battery of 10 neuropsychological tests performed in 100 randomly selected patients participating in the HALT-C clinical trial. The overall kappa between the 2 graders on level of impairment was 0.59. Clinician ratings (the gold standard) were similarly sensitive to identifying cognitive impairment as was classification based on standard scores (44% vs. 40%). Global Deficit Scores (GDS), derived from pooling standard scores, also identified 44% of patients as having mild impairment and were highly correlated with clinician ratings (r = .81 p = < 0.0001). Neither clinician ratings nor deficit scores correlated with SF-36 subscale or summary scores but did correlate with depression scores (p < .0007). In summary, clinician ratings and deficit scores identified a similar prevalence of cognitive impairment amongst CHC patients with advanced fibrosis. There was a significant correlation between cognitive impairment and self-reported depression.

Background/aims: Prior studies have demonstrated neuropsychological abnormalities in chronic hepatitis C (CHC) patients even with mild fibrosis. The aim of this study was to determine the frequency, type, and severity of cognitive impairment in a large group of CHC patients with advanced fibrosis., Methods: Ten validated neuropsychological tests were administered to 201 CHC patients. Standard scores for individual tests were calculated using normative population data that controlled for age, gender, and/or education. Lifetime psychiatric history, alcohol consumption, and mood status were also determined., Results: 33% of patients met criteria for cognitive impairment (i.e. standard score <40 on at least 4 tests). Mild impairment in verbal recall and working memory were noted with other domains remaining intact. Liver disease severity and lifetime psychiatric/substance abuse history did not correlate with group mean cognitive test results or the presence of cognitive impairment. In contrast, IQ and depression scores were significant and independent predictors of cognitive impairment (ROC = 0.84)., Conclusions: 33% of patients entering the HALT-C trial have evidence of a mild, non-focal subcortical processing deficit which was highly correlated with IQ, education, and occupation. Future studies of cognitive function in CHC patients should control for general cognitive ability.