Evidence for a cerebral effect of the hepatitis C virus

Forton, Daniel; Allsop, Joanna; Main, Janice; Foster, Graham R.; Thomas, Howard; Taylor‐Robinson, Simon D.

doi:10.1016/s0140-6736(00)05270-3

Cited by 308 publications

(287 citation statements)

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“…Other investigators have suggested that the presence of replicating HCV in the body and particularly in the brain may contribute to the high incidence of mood disorders, impaired cognition, and reduced quality of life reported in chronic hepatitis C patients compared to uninfected controls. 10,45,46 The lack of a correlation between HCV RNA suppression with objective measures of cognitive function in the current study may, in part, be due to the small number of patients enrolled or to the lack of a true biological effect of HCV replication on cognitive function. In patients with myeloproliferative disorders who are prothrombotic and have cognitive impairment, improved cognitive function has been reported following interferon treatment, presumably due to improved cerebral blood flow and oxygenation.…”

Section: Discussionmentioning

confidence: 80%

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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Section: Discussionmentioning

confidence: 80%

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

et al. 2007

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“…Single-voxel 1 H MRS examinations were performed using an automated PRESS sequence (repetition time, 1,500 milliseconds; echo time, 135 milliseconds; 128 acquisitions). 8 The …”

Section: Methodsmentioning

confidence: 99%

Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease

et al. 2002

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Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group ( C hronic hepatitis C (HCV) infection is estimated to affect 170 million people worldwide 1 and constitutes a major public health problem. It causes a fluctuating chronic hepatitis that may progress to cirrhosis and hepatocellular carcinoma. Attempts to understand the natural history of this infection have largely focused on the viral and host factors that predict progression of liver pathology from necroinflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Consequently, the decision to treat patients is normally based on an assessment of these factors, including staging of disease with a liver biopsy, 2 rather than on particular symptoms. There is, however, emerging literature suggesting that, even in the absence of clinically significant liver disease, chronic HCV infection causes a substantial reduction in quality of life 3 that improves following successful antiviral treatment. 4 These findings are in agreement with the clinical observation that patients with chronic HCV infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. 5,6 The etiology of these symptoms is unknown. The symptoms do not appear to be associated with the degree of hepatitis, the presence of autoimmune disorders 5 or cirrhosis, 3 a history of intravenous drug usage (IVDU), 3 or the level of circulating cytokines. 7 We have previously reported cerebral metabolite abnormalities in patients with histologically proven mild HCV infection using proton magnetic resonance spectroscopy ( 1 H MRS). 8 These abnormalities are similar to the 1 H MRS changes reported in cerebral human immunodeficiency virus (HIV) infection in both cognitively impaired 9,10 and asymptomatic individuals. 11 In this study, we address the hypothesis that HCV infection can result in cerebral dysfunction, which may underlie both the neuropsychological symptoms and the 1 H MRS abnormalities described. We used a cognitive assessment battery to determine whether cognitive impairment exists in patients with histologically defined mild chronic HCV infection and 1 H MRS to determine whether cerebral metabolite abnormalities are associated with impaired cognitive function.

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“…Neuropsychological tests, electrophysiological event-related potentials, and proton magnetic resonance spectroscopy ( 1 H MRS) have been used to investigate whether cerebral dysfunction exists in these patients even in the absence of severe liver disease. An initial study reported by Forton et al using 1 H MRS revealed elevated choline in the basal ganglia and cerebral white matter in a cohort of individuals with chronic HCV infection who had histologically mild liver disease, compared with individuals with hepatitis B and control subjects. 1 More recently, this group reported deficits in concentration and working memory speed in viremic patients with hepatitis C, and the degree of impairment was correlated with the level of choline.…”

mentioning

confidence: 96%

“…An initial study reported by Forton et al using 1 H MRS revealed elevated choline in the basal ganglia and cerebral white matter in a cohort of individuals with chronic HCV infection who had histologically mild liver disease, compared with individuals with hepatitis B and control subjects. 1 More recently, this group reported deficits in concentration and working memory speed in viremic patients with hepatitis C, and the degree of impairment was correlated with the level of choline. 2 Similar deficits in sustained attention and psychomotor speed have been reported in other studies, [3][4][5] and subclinical impairment in the P300 event-related potential has been described.…”

mentioning

confidence: 96%

“…6 Likewise, Forton et al reported no association between cognitive impairment and biochemical markers of liver disease activity as such (serum alanine aminotransferase). 1,2 Perhaps the most striking evidence of dissociation comes from the studies demonstrating elevated cholinecontaining compounds in the brain in patients with HCV, 1,2 because this is the opposite of the pattern seen in hepatic encephalopathy. 13,14 Given the few studies to date, the small sample sizes, and the lack of control over some of the potential confounding variables, our first aim in the present investigation was to employ rigorous screening criteria to exclude individuals with known risk factors for cognitive impairment.…”

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confidence: 99%

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

et al. 2005

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Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease-correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus-related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n ‫؍‬ 46) was also assessed.

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Evidence for a cerebral effect of the hepatitis C virus

Cited by 308 publications

References 4 publications

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

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

Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease

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

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