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). 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.

Neurocognitive Effects of the Hepatitis C Virus

“…Among HCV-positive individuals, only one study found minor impairment, whereas four other studies found this domain intact in individuals with HCV infection [18,21,37•,41•]. Cordoba et al [21] found verbal fluency impairments among HCV-positive individuals with decompensated cirrhosis.…”

Minimal hepatic encephalopathy matters in daily life

“…However, other studies have not demonstrated a difference in psychometric performance of cirrhotics with chronic hepatitis C compared to those without it [30,34] . In addition, a recent detailed study before and after interferon therapy in chronic hepatitis C cirrhotics failed to find an improvement or deterioration during and after therapy completion [35] . Diabetes mellitus is an important correlate of patients with cirrhosis, with the increasing importance of non-alcoholic steatohepatitis, and is also correlated with chronic hepatitis C in the general population [36] .…”

Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin

“…First, this study addresses major limitations of the previous longitudinal neurocognitive studies noted above. Few studies have taken into account naturally occurring change and practice effects on repeated neurocognitive test performance, which is a possible explanation of the diverging findings for past studies on both HCV/HIV co-infection (Giesen et al 2004; Ryan et al 2004; Clifford et al 2005; Hilsabeck and Castellon 2005; Hinkin et al 2008) and pegylated IFN/RBV treatment studies (Fried 2002; Hilsabeck and Hassanein 2005; Fontana et al 2007; Wobrock et al 2008; Fontana et al 2010; Group et al 2014; Huckans et al 2015). We controlled for practice effects by adopting the standard regression based approach, which utilized norms for change (McSweeny et al 1993; Hinton-Bayre 2010a; Maassen 2010; Hinton-Bayre 2010b; Cysique et al 2011).…”

“…Additionally, this study did not assess whether neurocognitive decline sustained or improved upon treatment discontinuation. Past research (e.g., Fontana et al (2007; 2010)) leads us to assume upon the discontinuation of IFN/RBV treatment neurocognitive functioning would likely be improved. Lastly, the introduction of direct acting antiviral therapy for the treatment of Hepatitis C has dramatically transformed the treatment of HCV among both mono- and co-infected patients such that IFN is no longer used.…”

“…Multiple longitudinal studies have found associations between IFN/RBV treatment and neurocognitive dysfunction, (Hilsabeck and Hassanein 2005; Majer et al 2008) whereas some studies have observed neurocognitive decline return to normal upon treatment completion (Kraus et al 2005; Fontana et al 2007), and others have not found a clear association between IFN treatment and cognition (Reichenberg et al 2005). A study by Huckans et al (2015) examined neurocognitive functioning over six months of 64 HCV mono-infected patients, 33 were treated with IFN/RBV and 31 were not treated.…”