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

Abstract

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.

Neuropsychological effects of direct‐acting antiviral treatment for Hepatitis C virus subjects: A systematic review

“…Bar et al 40 To assess the cognitive impairment of HCV-infected patients and its predictors, and determine whether it is reversible after successful DAA treatment.…”

“…The direct-acting antiviral agents (DAAs) are a set of medications used to treat patients infected by the HCV. The summary of study characteristics and quality assessment of the 12 [29][30][31][32][33][34][35][36][37][38][39][40] included studies are presented in Table 2. Two of them were considered high quality, whilst the remaining ten others had ratings ranging from 4 to 6 stars, suggesting moderate quality.…”

“…Nine of the studies only evaluated it at the end of DAAs treatment. 29,[31][32][33][34][35][38][39][40] The other studies evaluated it twice-during, soon after the end, or after the end of DAAs treatment. 30,36,37 Amongst the results related to the cognitive effect of DAAs treatment, some studies had one or two control groups of healthy subjects, subjects coinfected with HIV and/or subjects with another clinical condition.…”

“…After DAAs treatment, the HCV group had a significant improvement in the RAVLT, semantic and phonemic verbal fluency scores, and a shortening of about 15 ms for P300, suggesting a direct effect on the brain. Bar et al40 did not find significant differences between baseline and the evaluation three months after the end of DAAs treatment for the neuropsychological outcome, evaluated with Trail Making Test A and the Digit symbols test. The results for the critical flicker frequency (CFF) test-a neurophysiological measure of visual discrimination and general arousal, were positively significant.…”

Improvement of chronic HCV infection‐related depression, anxiety, and neurocognitive performance in persons achieving SVR‐12: A real‐world cohort study

“…7 The nervous system is an immune-privileged site that may explain the neurocognitive symptoms, depression and associated poor health-related quality of life (HRQoL) in persons living with HCV (PLHCV). 8,9 The presence of depression and cognitive impairment may affect medication adherence in patients on antivirals, although HCV clearance has been demonstrated to improve cognition in a recent metaanalysis. 10 Cognitive impairment has been noted as subtle changes in processing speed or reaction times, memory, performance tests for vigilance, attention, psychomotor speed and verbal fluency in up to 50% of PLHCV.…”