title: Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0362, USA. rfontana@med.umich.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: Linas A
authors.initials: LA
authors.lastname: Bieliauskas
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: Carla
authors.initials: C
authors.lastname: Back-Madruga
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Snow
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
authors.forename: Ziad
authors.initials: Z
authors.lastname: Kronfol
authors.forename: Latha
authors.initials: L
authors.lastname: Padmanabhan
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000523:psychology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a