Hepatitis C virus eradication improves immediate and delayed episodic memory in patients treated with interferon and ribavirin

Abstract

BackgroundChronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders.MethodA prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment.ResultsThirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR displayed significant improvement in immediate (p = 0.045) and delayed verbal episodic memory (p = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment (p = 0.719).ConclusionsEradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.

Neuroimaging Findings in Chronic Hepatitis C Virus Infection: Correlation with Neurocognitive and Neuropsychiatric Manifestations

“…There is less certainty on the chronic effect of this therapy. Although a normalization in basal ganglia inflammatory biomarkers on MRS in patients achieving SVR has been observed in both those groups with increased [42,48] and with decreased baseline values [41], in studies evaluating clinical outcomes opposing results of improvements on follow-ups in episodic memory, attention and phonemic verbal fluency [63], and also progressive worsening after treatment completion [59,62], have been observed. A possible explanation of these divergent outcomes relies on the influence on the cognitive domains of achieving SVR, and HIV serological status [59,63].…”

“…Regardless of SVR achievement, transient treatment-induced depression can be observed in up to half of the patients on medication. The disorder fades with treatment suspension, being persistent at 6 months from the end of the treatment in less than one patient in ten [63]. Risk of further recurrences of depressive episodes after the treatment course is higher in male patients and those aged above 60 years, more so in case of premorbid anxiety or depressive disorder [64].…”

Mechanisms of neuropathogenesis in HIV and HCV: similarities, differences, and unknowns

“…In one study, sustained virologic response (SVR) was associated with improvement in verbal episodic memory, selective attention, and phonemic fluency (Barbosa et al 2017). In another study, SVR did not improve neurocognitive performance compared to controls, but benefits were seen in a particular subgroup of responders who had improvements in their white matter integrity on neuroimaging (Kuhn et al 2017).…”

“…In HCV, the introduction of DAA was much more recent than cART, and subsequent follow-up is therefore less, but recent studies suggest that functional cure confers an improvement in neurocognitive function. In one study, sustained virologic response (SVR) was associated with improvement in verbal episodic memory, selective attention, and phonemic fluency (Barbosa et al 2017). In another study, SVR did not improve neurocognitive performance compared to controls, but benefits were seen in a particular subgroup of responders who had improvements in their white matter integrity on neuroimaging (Kuhn et al 2017).…”

Successful Antiviral Therapy Reduces Risk of Schizophrenia Among Chronic Hepatitis C Patients: A Nationwide Real-World Taiwanese Cohort (T-COACH)

“…Successful antiviral therapy with pegylated-interferon (IFN) plus ribavirin has been associated with long-term benefits for patients with HCV, in terms of risk reduction in liver-related as well as extrahepatic complications, including hepatocellular carcinoma, liver failure, cardiovascular events, diabetes, and end-stage renal diseases [ 13–17 ]. This therapy, through the achievement of sustained virological response (SVR), could improve attentional and neurocognitive functions [ 18 , 19 ]. However, the therapy did not affect the short-term frequency of depressive disorders [ 19 ].…”