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Re: Brain Fog - Study Reports Hepatitis C Impairs Cognitive Functioning: memory, concentration, depression

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  • claudine intexas
    (Repost) NATAP - www.natap.org ... Study Reports Hepatitis C Impairs Cognitive Functioning: memory, concentration, depression This article is published in the
    Message 1 of 1 , May 20, 2002
      NATAP - www.natap.org

      Study Reports Hepatitis C Impairs Cognitive Functioning: memory,
      concentration, depression

      This article is published in the current issue of the journal called
      Hepatology. The authors report their findings from a small
      preliminary study. They recommend further study is needed to confirm
      their findings. These authors report patients in their HCV clinic who
      have HCV appear to have cognitive impairment and more fatigue,
      depression, less concentration ability, and less memory ability. The
      authors caution this is a small preliminary study. They also caution
      that study bias is possible because these patients were referred to
      the HCV clinic and so they may not represent all patients such as
      those not referred to the clinic. Clinic referrals may be sicker. The
      authors suggest two possible explanations for these symptoms: (1) HCV
      may directly infect the brain similarly to the way HIV infects the
      brain, (2) HCV may stimulate the immune system in a way that
      dysregulates cytokine functioning causing these cytokines to be able
      to enter the brain and cause dysregulation; this is discussed further
      near the end of the article. These study findings are consistent with
      reports from some patients with HCV, that they experience fatigue,
      anger, hostility, anxiety and depression, and that they feel its
      associated with having HCV. But, this association has not been well
      studied. This study was first reported at liver meetings two years
      ago. In addition other studies have reported similar findings. Here
      are a few links to these studies, and related articles:

      Assessment of Fatigue and Psychologic Disturbances in Patients with
      Hepatitis C Virus Infection

      HCV and Brain Dysfunction (report of this study at liver conference 2
      years ago)

      HCV and Fatigue

      Abstract: 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
      (HCV+) 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 (mean
      [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P = .02).
      A factor analysis showed impairments in power of concentration and
      speed of working memory, independent of a history of intravenous drug
      usage (IVDU), depression, fatigue, or symptom severity. A subgroup of
      17 HCV-infected patients also underwent cerebral proton magnetic
      resonance spectroscopy (1H MRS). The choline/creatine ratio was
      elevated in the basal ganglia and white matter in this group.
      Patients who were impaired on 2 or more tasks in the battery had a
      higher mean choline/creatine ratio compared with the unimpaired
      patients. In conclusion, these preliminary results demonstrate
      cognitive impairment that is unaccounted for by depression, fatigue,
      or a history of IVDU in patients with histologically mild HCV
      infection. The findings on MRS suggest that a biological cause
      underlies this abnormality. (HEPATOLOGY 2002;35:433-439.)

      The HCV-infected group scored significantly worse on the power of
      concentration (P = .001) and on the speed of memory processes (P =
      .001) factor scores than the healthy controls.

      With respect to the affective scores, the HCV-infected group scored
      worse on the Hospital Anxiety and Depression Scales.

      There were no statistically significant differences in the subjects'
      assessment of fatigue in either the physical or mental domains,
      although there was a trend toward increased fatigue in the
      HCV-infected group. Similarly, with respect to the SF-36
      quality-of-life scale, there were no differences between the 2 groups
      in the mental summary score. However, there was a significant
      difference in the physical summary score (P = .006), with lower
      ratings in the HCV-infected group.

      Comments By Study Authors

      These preliminary findings are consistent with cognitive and cerebral
      1H MRS metabolite abnormalities in patients with histologically
      defined mild hepatitis due to HCV infection. The data support the
      clinical impression and assertions of many HCV-infected patients that
      they are cognitively impaired (���brain fog���). However, the
      mechanism underlying these findings remains to be defined.

      The HCV-infected patients were found to be more depressed than the
      HCV-cleared group, as has been previously reported. There were no
      statistically significant correlations between the cognitive factor
      scores that were abnormal in the HCV-infected group and the
      depression scores, indicating that impairment on these tasks is
      unlikely to be secondary to depression. Furthermore, if depression
      was the sole explanation for cognitive impairment in the HCV-infected
      patients, it is unlikely that it would cause the selective cognitive
      impairments that we report.

      A number of explanations may account for or contribute to the
      cognitive dysfunction observed in HCV-infected patients, including
      (1) a biological effect of HCV infection on the central nervous
      system, (2) the effect of personality or HCV acquisition-associated
      factors such as a history of IVDU, (3) the effect of affective
      disorders such as depression, or (4) the effect of subjectively
      experienced symptoms such as fatigue. It should be noted that these
      explanations are not necessarily mutually exclusive and might

      Patients with significant fibrosis or cirrhosis were excluded from
      the study, thereby excluding minimal hepatic encephalopathy as the
      cause of the abnormalities.

      A history of serious drug usage that had stopped at least 2 years
      before participation in the study (and in most cases much earlier)
      did not have an impact on cognitive performance, regardless of HCV

      The factor score analysis suggests that concentration and working
      memory processes may be preferentially impaired. These scores are
      derived from the summation of the reaction times on various tasks. We
      considered that the abnormalities might simply be a reflection of
      pure motor slowing as a result of a peripheral neuromuscular
      abnormality, but there were no differences in the simple reaction
      time between the 2 groups indicating impairment of central cognitive
      processes. Similar findings of slowed processing speed and impaired
      working memory are the most prominent features of cognitive
      dysfunction in patients with chronic fatigue syndrome. Such findings
      have also been reported in the medically asymptomatic stages of HIV
      infection and are consistent with the involvement of subcortical or
      frontostriatal brain systems.

      Although every attempt was made to prevent selection bias in this
      study, we accept that the study populations may not be wholly
      representative of the HCV-infected population because they were drawn
      from a tertiary referral HCV clinic. In particular, it is possible
      that patients with worse symptoms, both physical and psychological,
      are more likely to attend the clinic. Conversely, the exclusion of
      patients who were taking antidepressants, comprising 20% of the
      initial recruits and possibly those HCV-infected patients who were
      most likely to have cognitive dysfunction, may have led to an
      underestimation of the level of cognitive impairment. The purpose of
      this study was to investigate whether cognitive dysfunction is a
      feature of HCV infection, whereas larger studies will be required to
      estimate the prevalence.

      What may be the cause?

      Using 1H MRS, the authors reported finding an increase in the basal
      ganglia and whitematter choline/creatine ratio in patients with
      chronic HCV infection.

      Similar metabolite abnormalities in the same spatial distribution as
      those reported here have been extensively documented in cerebral HIV
      infection, both in neurosymptomatic and neuroasymptomatic
      individuals. In the case of HIV, infection of cerebral microglia,
      possibly via infected monocytes entering the brain, and subsequent
      microglial activation are believed to underlie the MRS changes. This
      raises the prospect that the metabolite abnormalities reported in
      this study are due to direct infection of the brain by HCV. The
      concept of extrahepatic replication of HCV is not novel, with several
      lines of evidence suggesting that peripheral blood mononuclear cells
      are infected. Microglia comprise up to 20% of all glial cells and are
      developmentally derived from bone marrow precursors of monocytic
      lineage. It is believed that resident microglia turn over slowly and
      are replaced by circulating monocytes. It is therefore possible that
      HCV may be introduced to the central nervous system via infected
      monocytes, through a ���trojan horse��� mechanism.

      An alternative explanation for our findings is a centrally mediated
      effect of peripherally derived cytokines that may cross the
      blood-brain barrier. Although cytokines are large peptides, animal
      studies have demonstrated passage of cytokines including tumor
      necrosis factor , interferons alfa and gamma, and interleukins (IL) 1
      and 1 across the blood-brain and blood-spinal cord barriers.
      Alternatively, peripherally derived cytokines may bind to the
      cerebral vascular endothelium, inducing the generation of secondary
      messengers. Intracerebral cytokines have been associated with
      immunologic, neurochemical, neuroendocrine, and behavioral
      activities. Indeed, treatment with interferon alfa is associated with
      a constellation of symptoms, including depression and reports of
      memory impairment and cognitive slowing. Whether elevated endogenous
      cytokines in chronic inflammatory and infective conditions exert a
      significant cognitive effect is unclear. Several studies have
      reported elevated levels of circulating cytokines, including IL-1,
      IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor, in chronic HCV
      infection; however, a recent study found no correlation between
      levels of circulating IL-1, IL-6, tumor necrosis factor, and fatigue
      in chronic HCV infection.

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