Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors

McAndrews, Mary Pat; Farcnik, Karl; Carlen, Peter L.; Damyanovich, A.; Mrkonjic, Mirela; Jones, Susan; Heathcote, E. Jenny

doi:10.1002/hep.20635

Cited by 183 publications

(231 citation statements)

References 35 publications

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“…The therapeutic response to antiviral treatment for neuropathies is generally unsatisfactor y [172] . Furthermore, fatigue or depression is found in many patients with chronic HCV infection, with incidences of about 50% and 35%, respectively [173][174][175] . These neurocognitive dysfunctions have been characterized epidemiologically or pathophysiologically in chronic HCV infection [166,167,176] , and may be explained by the neuroinvasion of HCV, because HCV has been reported to be found in monocytes/microglia of the central nervous system [176,177] .…”

Section: Polyneuropathy and Neurocognitive Dysfunctionmentioning

confidence: 99%

Systemic abnormalities in liver disease

Minemura¹,

Tajiri²,

Shimizu³

2009

WJG

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Section: Polyneuropathy and Neurocognitive Dysfunctionmentioning

confidence: 99%

Systemic abnormalities in liver disease

Minemura¹,

Tajiri²,

Shimizu³

2009

WJG

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“…[8][9][10] The cause of these abnormalities is not known; however, possibilities include a direct effect of HCV, which may replicate in neurons as well as the effects of systemic cytokines, concomitant psychiatric disease, and subclinical hepatic encephalopathy. 11 The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial (HALT-C) is a prospective multicenter study designed to investigate the potential benefit of maintenance therapy with peginterferon in reducing the rate of clinical outcomes in prior nonresponders with advanced fibrosis. 3,12 Initially, all patients were treated with peginterferon alfa-2a and ribavirin for 24 weeks in the "lead-in phase."…”

mentioning

confidence: 99%

Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C

et al. 2007

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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.

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“…This has been well demonstrated for patients with HIV, who can demonstrate elevations of brain inflammatory mediators in the absence of overtly encephalitic pathologies (Glass et al, 1993). Importantly, in some magnetic resonance spectroscopy (MRS) studies of HCV monoand HIV/HCV-coinfected patients, there has been evidence of white matter inflammation as indicated by increased choline neurometabolites (McAndrews et al, 2005;reviewed in Forton et al, 2006).…”

Section: Discussionmentioning

confidence: 93%

“…There is evidence to suggest that it may replicate within the central nervous system (CNS), with detection of negative-strand replication intermediates and brain-specific quasispecies in a handful of patients reported to date (Forton et al, 2004a;Radkowski et al, 2002;Vargas et al, 2002). A separate body of work is growing to determine whether patients with clinical evidence of HCV (as determined by positive serology for anti-HCV antibodies or plasma viral load) have CNS dysfunction either caused or worsened by presence of the virus (Forton et al, 2004b;Hilsabeck et al, 2002;McAndrews et al, 2005;Ryan et al, 2004). However, although multiple lines of evidence are converging to delineate a neurobiology, it is currently unclear how commonly HCV can be found in brain, what factors promote brain invasion, and what the clinical sequellae of this brain invasion may be.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathologic correlates of hepatitis C virus in brain: A pilot study

et al. 2008

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Hepatitis C virus (HCV) has been detected in the brain tissues of 10 individuals reported to date; it is unclear what clinical factors are associated with this, and with what frequency it occurs. Accordingly, a pilot analysis utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) to detect and sequence HCV in premortem plasma and postmortem brain and liver from 20 human immunodeficiency virus (HIV)-infected and 10 HIV-naïve individuals was undertaken. RNA encoding the first 126 amino acids of the HCV E1 envelope protein and the majority of the E1 signal sequence was analyzed in parallel with an 80-base-long segment of the 5′ untranslated region (UTR). Liver HCV was detected only in subjects with premortem HCV viremia (10 HIV-infected and 3 HIVnaïve). Brain HCV was detected in 6/10 HCV/HIV-coinfected and 1/3 HCV-monoinfected subjects. In the setting of HIV, the magnitude of plasma HCV load did not correlate with the presence of brain HCV. However, coinfected patients with brain HCV were more often off antiretroviral therapy and tended to have higher plasma HIV loads than those with HCV restricted to liver. Furthermore, premortem cerebrospinal fluid (CSF) analysis revealed that HCV/HIV-coinfected patients with brain HCV had detectable CSF HIV, whereas those without brain HCV had undetectable CSF HIV loads (P = .0205). Neuropsychologic tests showed a trend for hierarchical impairment of abstraction/ executive functioning in HIV/HCV coinfection, with mean T scores for HIV monoinfected patients 43.2 (7.3), for liver-only HCV 39.5 (9.0), and for those with HCV in brain and liver 33.2 (5.1) (P = . 0927). Predominant brain HCV sequences did not match those of the plasma or liver in 4 of the 6 coinfected patients analyzed. We conclude that in the setting of HIV/HCV coinfection, brain HCV is a common phenomenon unrelated to the magnitude of HCV viremia, but related to active HIV disease and detectable CSF HIV. Furthermore, there is sequence evidence of brain compartmentalization. Differences in abstraction/executive function of HCV/HIV coinfected patients compared to HIV monoinfected warrant further studies to determine if neuropsychiatric effects are predicated upon brain infection.

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Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors

Cited by 183 publications

References 35 publications

Systemic abnormalities in liver disease

Systemic abnormalities in liver disease

Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C

Clinicopathologic correlates of hepatitis C virus in brain: A pilot study

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