Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C


  • This is publication number 22 from the HALT-C Trial Group.

  • Potential conflict of interest: Dr. Fontana is in the speakers' bureau of Roche Pharmaceutical and Bristol-Myers Squibb. Dr. Lindsay received grants from and advises for Hoffmann-LaRoche, Inc., and Valeant Pharmaceuticals. She also received grants Schering-Plough Corp., Scripps Clinic Liver Research Consortium, and Idenix Pharmaceuticals, Inc. She advises for Gilead Sciences, Roche Diagnostics, Quest Lab., Amgen Corporation, Invesek, Bristol Myers Squibb, Charles River Lab., iMedOptions, Zymogenetics, Inc., Peregrine Pharmaceuticals, Inc., and Kendle International. She is a consultant for Fujisawa Research Institute of America, Inc., GlaxoSmithKline, Wellpoint Pharmacy Management, Aventix Pharmaceuticals, Inc., and Medtronics.


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. (HEPATOLOGY 2007;45:1154–1163.)