Is psychosocial and cognitive dysfunction misattributed to the virus in hepatitis C infection? Select psychosocial contributors identified

Abstract

Chronic hepatitis C is associated with health-related quality of life and cognitive impairments, even in mild disease. Recent evidence demonstrating hepatitis C virus (HCV) neurotropism has strengthened a neuropathophysiological hypothesis. However, sample heterogeneity confounds study outcomes. A uniquely homogeneous cohort of Irish women, following an iatrogenic HCV outbreak, offers a rare opportunity to control for HCV chronicity and the virus' purported impact on quality of life and cognition. A multi site, three-group, cross-sectional design was employed. Noncirrhotic, iatrogenically infected women, developing either acute or chronic infection, were recruited from prospective tertiary-care liver clinics and the community. Well-matched healthy controls were also recruited. All participants completed a psychosocial survey and were invited to undergo a comprehensive neuropsychological test battery. Significantly distressed psychosocial symptom profiles were observed in those with an iatrogenic HCV exposure history, which was independent of viral chronicity. Chronic and cleared HCV cohorts were not differentiated from each other. Two distinct subgroups, demarcated along 'impaired' vs 'nonimpaired' quality-of-life reports, were clearly identified and logistic regression analysis identified depressed mood and cognitive fatigue, rather than viral status, as statistically significant predictors of group membership. Compared with matched controls, significant cognitive impairments were not observed in either HCV cohort. Our findings provide strong evidence of nonviral factors accounting for quality of life impairment in chronic HCV and they also appear to question existing reports of cognitive dysfunction in mild disease. Depressed mood and cognitive fatigue appear to be critical psychosocial mediators of reduced quality-of-life and we hypothesize that metabolite abnormalities reported in HCV samples may also be confounded by these factors, given the associated literature.

Hepatitis C virus‐related symptoms, but not quality of life, were improved by treatment with direct‐acting antivirals

“…Additionally, HCV‐related encephalopathy is not correlated with viral status but is correlated with cognitive dysfunction and sleep disturbance . Because poor sleepers after SVR are at risk of HCV‐related encephalopathy, HCV‐cleared patients should be followed up.…”

Improvements in brain and behavior following eradication of hepatitis C

“…Accordingly, deficits in attention, concentration, psychomotor speed, and verbal fluency among HCV+ individuals have been most frequently reported (Hilsabeck et al 2003; Hinkin et al 2008; Letendre et al 2007; Clifford et al 2009; Soogoor et al 2006; Thein et al 2007). However, other studies (e.g., Lowry et al 2016; McAndrews et al 2005) have failed to detect neurocognitive deficits associated with HCV infection (e.g., Lowry et al 2016). These studies have generally paid close attention to potentially confounding causes of impairment, such as injection drug use (Zeuzem 2008), history of head trauma (Kraus et al 2013), and HCV RNA levels (e.g., Forton et al 2002; Kraus et al 2013; Lowry et al 2016).…”

“…However, other studies (e.g., Lowry et al 2016; McAndrews et al 2005) have failed to detect neurocognitive deficits associated with HCV infection (e.g., Lowry et al 2016). These studies have generally paid close attention to potentially confounding causes of impairment, such as injection drug use (Zeuzem 2008), history of head trauma (Kraus et al 2013), and HCV RNA levels (e.g., Forton et al 2002; Kraus et al 2013; Lowry et al 2016). As a result, there is not a clear consensus regarding the impact of HCV-associated neurocognitive and neurobehavioral effects.…”

“…SVR has been shown by some studies (Bladowska et al 2013b; Forton et al 2002) though not all (e.g., Huckans et al 2016; Lowry et al 2016; McAndrews et al 2005) to result in improvement in neurocognitive performance. While the mechanism remains unclear, there is reason to believe that successful treatment of HCV could result in improved neurocognitive function, though it remains possible that some of the improvements may be attributable to the nature of open-label trials and/or practice effects associated with repeat testing, for example.…”

HCV encephalopathy – an artefact due to medical care?

“…This ‘neuropathophysiological model of HCV‐related HRQoL and cognitive dysfunction’ – as they call it – is put into question – not by their data but by their interpretation – in the paper by Lowry and colleagues published in this volume of the Journal of Viral Hepatitis . Lowry et al .…”