Hepatitis C related cognitive impairment: Impact of viral and host factors and response to therapy

Nir Bar, Sharon Levy, Liat Deutsch, Moshe Leshno, Liane Rabinowich, Fadi Younis, Oren Shibolet, Helena Katchman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Chronic hepatitis C virus (HCV) infection is associated with cognitive impairment via several suggested mechanisms including direct neurotoxicity and minimal hepatic encephalopathy. The prevalence of HCV-related cognitive impairment and whether it is reversed by anti-viral therapy is unknown. We aimed to assess predictors and reversibility of cognitive impairment of HCV-infected patients after successful treatment. Consecutive HCV patients treated during the EMERALD study (AbbVie 3D regimen for protease inhibitors failure) underwent neuropsychological (number connection test A [NCTA] and digital symbol test [DST]) and neurophysiological (critical flicker frequency [CFF]) tests at baseline and at 12 weeks post-treatment. Patient self-reported outcomes (PROs) were prospectively collected. Patients with a history of hepatic encephalopathy were excluded. Thirty-two patients underwent the cognitive tests at baseline. Seven of them had abnormal CFF test findings. Twenty-five (25/32, 78%) patients had repeated evaluations 3 months post-treatment. High viral loads were significantly associated with abnormal CFF across fibrosis levels (area under the ROC curve 0.817). CFF results significantly improved following viral eradication, from 40.9 (interquartile range 38.6–42.9) at baseline to 41.5 (39.8–44), p =.042, at follow-up. Both NCTA and DST results improved, but not significantly. There was improvement in the PROs of general health perception and vitality. The NCTA and DST results were more significantly associated with PROs than CFF. This prospective interventional study showed greater cognitive impairment in HCV patients with high viral load and demonstrated partial reversibility of HCV neurotoxicity and subsequent improvement in PROs following treatment.

Original languageEnglish
Pages (from-to)870-877
Number of pages8
JournalJournal of Viral Hepatitis
Issue number6
StatePublished - Jun 2021


FundersFunder number


    • cognitive dysfunction
    • direct-acting antiviral
    • hepatitis C virus
    • minimal hepatic encephalopathy
    • patient-reported outcomes measures


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