Elsevier

Journal of Hepatology

Volume 41, Issue 5, November 2004, Pages 845-851
Journal of Hepatology

Hepatitis C virus infection affects the brain—evidence from psychometric studies and magnetic resonance spectroscopy

https://doi.org/10.1016/j.jhep.2004.07.022Get rights and content

Background/Aims

Up to 50% of patients infected with the hepatitis C virus (HCV) complain of chronic fatigue and difficulties in concentration and memory. The aim of the present study was to seek evidence for the presence of central nervous system involvement in HCV infected patients with only mild liver disease.

Methods

Thirty HCV infected patients with normal liver function, 15 of whom were identified as having mild and 15 moderate to severe fatigue using the fatigue impact scale, underwent neurological and neuropsychological examination, electroencephalography (EEG) and cerebral proton magnetic resonance imaging (MRI) and spectroscopy (MRS). Fifteen healthy volunteers, matched for age and educational attainment, served as controls.

Results

In comparison to the healthy controls the patients with HCV infection showed evidence of cognitive impairment, primarily attention and higher executive functions, higher levels of anxiety and depression and impairment of quality of life. In addition they showed a significant decrease of the N-acetyl-aspartate/creatine ratio in the cerebral cortex on 1H MRS while the EEG was slowed in 25%. In general the deficits were more marked in the patients with moderate rather than mild fatigue.

Conclusions

The data provide evidence of central nervous system involvement in patients with HCV infection.

Introduction

Approximately 50% of patients infected with the HCV virus complain of fatigue, the occurrence of which is independent of the degree of liver damage, the viral load, or the presence of concomitant autoimmune disorder [1], [2], [3]. The presence of fatigue has a significant deleterious effect on quality of life in such patients and is an important contributory factor in premature retirement [4], [5], [6], [7].

Very little information is available on the pathophysiology of the fatigue observed in patients with HCV infection with minimal liver disease. Recently it has been hypothesized that these patients may develop an encephalitis similar to that observed in patients with HIV infection [8]. This assumption is based on the findings on cerebral proton magnetic resonance spectroscopy (MRS), by Forton et al. [9], [10], [11], of alterations in brain metabolites in patients with hepatitis C similar to those observed in patients infected with HIV. These authors also found evidence of impairment in psychometric performance in these patients, which was confirmed by Hilsabeck et al. [12] but not by Cordoba [13], although this might be a function of the test battery used [14]. Kramer et al. [15] showed a significant increase of the P300 latency in patients with hepatitis C who had little or no evidence of significant liver injury but few if any other electrophysiological studies have been undertaken in this patient population. Thus, there is increasing evidence that hepatitis C infection is associated with significant cerebral dysfunction in at least a percentage of patients.

The aim of the present study was to elucidate whether patients' subjective impression of fatigue was accompanied by objective evidence of cerebral dysfunction by use of a comprehensive neurological and neuropsychological assessment, electroencephalography (EEG), and cerebral magnetic resonance imaging (MRI) and spectroscopy (MRS).

Section snippets

Patients and methods

A total of 100 patients with HCV infection who attended the outpatient clinic of the Department of Gastroenterology, Hepatology and Endocrinology of the Medizinische Hochschule in Hannover were approached, by letter, and asked first, to fill in the fatigue impact scale (FIS) [16] and second, to state their willingness, if eligible, to take part in a study aimed at detecting cerebral complications of hepatitis C. The severity of their HCV-related liver injury was assessed (AS, KB) on the basis

Results

There were no significant differences in age, gender, years of education and overnight sleeping time between the patients and control subjects (Table 2). The FIS scores were significantly higher in both patient groups than in the healthy controls (controls: range 0–23, median: 5, mean 7.4±8,1; mildly-fatigued patients: range 0–43, median: 20, mean: 21.5±12,8; moderately fatigued patients: range 50–132, median: 70, mean: 79.8±25.6; P<0.005); the scores in the two patient populations differed

Discussion

The 30 patients included in the present study had HCV infection but little or no liver disease. None had abnormal liver function tests; none showed radiological evidence of cirrhosis and none of the 14 patients who underwent liver biopsy showed histological evidence of significant liver injury. The investigations undertaken as part of the study provided additional confirmation that the patients did not have significant liver injury as none showed evidence of motor disturbance on psychometric

Acknowledgements

This study has been supported in part by a grant from the Medizinische Hochschule Hannover (HiLF-Projekt). The authors wish to thank Dr Marsha Morgan and Mrs Elinor Switzer for critically reading and correcting the manuscript.

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  • Cited by (0)

    Some of the data presented in this paper have been published previously in abstract form.

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