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Fatigue and Anger in HCV

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  • claudine intexas
    Note: If you would like the complete 5 page study let me know - I can email it to you as an attachment. Just send me an email at claudineintexas@yahoo.com
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      Note: If you would like the complete 5 page study let
      me know - I can email it to you as an attachment. Just
      send me an email at claudineintexas@... (Don't
      send it to the GIWorld address.)
      Claudine


      NATAP - www.natap.org
      Jules Levin

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

      Here are a few excerpts from this study followed by
      the study Abstract
      and a
      discussion of the study & study results.

      --This study finds feelings of anger and hostility
      were significantly
      greater
      in patients with chronic HCV infection, whether they
      were completely
      abstinent or indulging in heavy alcohol use compared
      with patients
      with
      non-liver chronic systemic illnesses.

      The impact of fatigue on the individual in the form of
      interference
      with
      physical activity or mental concentration was
      significantly greater in
      patients with HCV infection compared with the other
      study groups.
      Moreover,
      the physical and mental effects of fatigue, such as
      worsening lethargy
      and
      reduction in motivation, were also increased in
      HCV-infected
      individuals.

      The most significant difference was observed with
      respect to
      depression, in
      which the scores were significantly greater in
      patients with chronic
      HCV
      infection, dual liver disease, and alcoholic liver
      disease than in the
      non-liver controls.

      The direct effect of HCV infection can be tested by
      assessing patients
      before
      and after antiviral therapy. Recent studies have shown
      that successful
      elimination of the virus is accompanied with
      improvement in quality of
      life
      scores; the extent of improvement was directly related
      to sustained
      virologic
      and biochemical responses to treatment. Conversely,
      nonresponders
      showed
      either a less-pronounced benefit or had a significant
      decline in
      quality of
      life.

      The pathogenesis of fatigue is unclear, and several
      factors have been
      incriminated. Excessive production of cytokines such
      as interferon,
      interleukin-1, and tumor necrosis factor- may be
      involved in the
      development
      of chronic fatigue syndromes. Some studies have noted
      elevated cytokine
      levels in patients with chronic liver disease, whereas
      others have
      found no
      causal link between cytokines and fatigue.
      It has been suggested that the reduction in quality of
      life scores
      found in
      HCV infection may be attributable to factors such as
      psychiatric
      disturbances
      associated with previous or current substance abuse.

      Our results show that the fatigue experienced by
      HCV-infected patients
      is not
      only more severe but also is more intransigent,
      responding less well to
      relieving factors such as rest and sleep. Our findings
      have important
      therapeutic implications because effective treatment
      of the psychologic
      disturbances may improve patients' fatigue and, thus,
      may have a
      beneficial
      impact on the quality of life of patients with HCV.
      ------------------
      Jagdeep Obhrai, M.D.; Yoshio Hall; B. S. Anand, M.D.

      From the Digestive Diseases Section, Baylor College of
      Medicine (J.O.,
      Y.H.,
      B.S.A.), Houston, Texas, U.S.A.; and Veterans
      Administration Medical
      Center
      (B.S.A.), Houston, Texas, U.S.A.

      JOURNAL OF CLINICAL GASTROENTEROLOGY 2001;32:413-417

      Abstract

      Background: It is a common clinical impression that
      fatigue is a
      frequent,
      and often debilitating, symptom in patients with
      chronic hepatitis C
      virus
      (HCV) infection. However, despite its obvious clinical
      importance,
      several
      aspects of fatigue,
      including its relationship with the underlying liver
      disease and the
      presence
      of psychologic disturbances, have not been well
      examined.

      Goals: The current study was carried out to assess
      these issues.

      Study: A total of 149 subjects were included in the
      study and were
      assigned
      to one of the following study groups: healthy controls
      (31), chronic
      HCV
      infection (24), combined HCV infection and chronic
      alcohol abuse (32),
      alcoholic liver disease
      (22), and chronic non-liver diseases (40). All
      subjects were
      administered
      investigator-assisted questionnaires designed to
      analyze the presence
      and
      severity of fatigue and psychologic abnormalities.

      Results: The mean (��SD) fatigue scores in patients
      with chronic HCV
      infection
      (140 �� 22.9; p = 0.002), alcoholic liver disease (127
      �� 31.4; p <
      0.001),
      mixed (HCV/alcoholic) liver disease (131 �� 29.0; p <
      0.001), and
      chronic
      non-liver
      diseases (128 �� 35.9; p = 0.004) were significantly
      greater compared
      to with
      healthy subjects (101 �� 31.8). The total fatigue
      scores were higher in
      HCV-infected subjects compared with the other patient
      groups, but the
      differences failed to
      reach statistical significance. Moreover, the fatigue
      experienced by
      patients
      with HCV did not improve with rest as effectively as
      in the other study
      groups. All patient groups had higher scores for
      psychologic
      disturbances
      compared with healthy subjects.

      Conclusions: The current study shows that fatigue and
      psychologic
      disturbances occur frequently in chronic diseases. The
      fatigue
      experienced by
      patients with HCV infection is more severe and
      intransigent and
      responds
      poorly to relieving factors. Moreover, patients with
      HCV infection are
      more
      depressed and harbor greater feelings of anger and
      hostility compared
      with
      those with non-liver chronic diseases. These
      observations are important
      because proper management of the psychologic symptoms
      may have a
      favorable
      impact on the quality of life of patients with HCV
      infection.

      -------------------------

      Background

      Hepatitis C virus (HCV) infection is one of the major
      causes of liver
      disease
      in the United States and around the world. A
      population-based serologic
      study
      suggested that 1.8% of the general population in the
      United States has
      antibodies to HCV.1 Acute infection with HCV is
      generally a mild
      illness
      compared with other viral causes of hepatitis;
      however, unlike other
      viral
      hepatititides, the infection usually fails to resolve
      spontaneously and
      the
      majority of individuals (approximately 80%) become
      chronically
      infected.2
      Liver disease in subjects with chronic infection is of
      variable
      severity. It
      usually runs a protracted and often an insignificant
      course for
      prolonged
      periods, but about 20% of individuals experience a
      progressive illness
      with
      the development of cirrhosis, hepatic decompensation,
      and
      hepatocellular
      carcinoma.2,3 In addition, HCV infection is associated
      with a variety
      of
      extrahepatic syndromes, including essential mixed
      cryoglobulinemia and
      membranoproliferative glomerulonephritis.4���6 With
      nearly 4 million
      Americans
      and 100 million individuals worldwide currently
      infected, HCV infection
      is
      likely to become an even greater global public health
      and economic
      problem in
      the future.

      Patients with chronic HCV infection typically have few
      symptoms, and
      most of
      these are mild and nonspecific. The most frequent
      symptom is fatigue,
      which
      is commonly described by the patient as malaise,
      lethargy, or poor
      energy
      level. In some patients, fatigue becomes all-pervasive
      and has an
      important
      impact on the quality of life. Despite its obvious
      clinical importance,
      several aspects of fatigue in hepatitis C remain
      controversial.
      Although some
      studies have shown that patients with hepatitis C have
      higher fatigue
      scores
      and reduced health-related quality of life compared
      with healthy
      controls,7���10 other studies did not find many
      differences between
      patients
      with hepatitis C and other subjects, including healthy
      blood donors who
      served as controls.2,3 Treatment with interferon
      either has been shown
      to
      have no effect on the health status measures11 or has
      resulted in
      significant
      improvement in the health-related quality of
      life.10,12,13 Moreover,
      the
      influence of psychologic disturbances on the fatigue
      experienced by
      patients
      with HCV has not been clearly examined. Thus, it is a
      real clinical
      challenge
      to not only characterize the presence and intensity of
      fatigue but also
      determine the association of fatigue with the
      comorbidities that are
      present
      in most chronic illnesses, such as the fear and
      anxiety of illness,
      tensions
      about transmitting infection to others and the
      possibility of future
      complications, and death.

      The objectives of our study were 2-fold. One, we
      wanted to determine
      whether
      the fatigue experienced by patients infected with
      hepatitis C is truly
      more
      severe than that in patients with liver diseases not
      related to HCV
      infection
      and non-hepatic
      chronic systemic illnesses. Second, we wanted to
      assess the association
      of
      fatigue with psychologic disturbances, which occur
      frequently in this
      group
      of patients, given their past or current history of
      alcohol and
      substance
      abuse.

      MATERIALS AND METHODS

      Diagnostic Instruments

      The study was conducted on a predominantly male
      population of 149
      patients at
      the Houston Veterans Administration Medical Center
      (Houston, TX,
      U.S.A.). The
      patients were administered interviewer-assisted
      questionnaires: one to
      quantify and characterize fatigue and another to
      assess the impact of
      fatigue
      on the quality of life. The 29-item Fatigue Assessment
      Instrument
      provided a
      global severity scale, as well as information
      regarding the triggers
      and
      pacifiers of fatigue.14 The Fatigue Assessment
      Instrument measured the
      current symptom profile of each subject; the
      sensitivity and
      specificity of
      this survey is more than 80% in assessing clinically
      relevant
      fatigue.14 The
      65-item Sickness Impact Profile assessed the impact of
      fatigue on a
      subject's
      daily functioning, with particular emphasis on
      psychologic parameters
      such as
      anxiety and depression. During the administration of
      the
      questionnaires,
      medically trained interviewers were blinded with
      regard to the
      patient's
      diagnosis. Detailed clinical evaluations and
      laboratory studies were
      performed on all patients to allow comparison of
      hepatic dysfunction
      with
      symptom severity.

      Study Subjects

      Five groups of subjects were included in the study.
      The chronic
      hepatitis C
      group consisted of 24 patients, all of whom had
      anti-HCV antibodies
      detected
      by the second generation recombinant immunoblot assay
      test (RIBA-II).
      All of
      these subjects
      completely abstained from alcohol use and had serum
      transaminase levels
      elevated above the upper limit of normal. The
      alcoholic liver disease
      group
      consisted of 22 patients who had a history of chronic
      alcohol abuse,
      defined
      as consumption
      of six drinks a day or more (80 g of ethanol/d) for
      more than 5 years,
      and in
      whom serum antibodies to HCV were negative by the
      RIBA-II test.
      Patients with
      dual liver disease consisted of 32 patients with a
      history of chronic
      alcohol
      use (
      80 g of ethanol/d for more than 5 years), detectable
      serum antibodies
      to
      HCV by the RIBA-II test, and elevated serum
      transaminase levels. All of
      the
      patients in the HCV-infected group, alcoholic liver
      disease group, and
      dual
      liver diseases group were negative for other causes of
      chronic liver
      disease
      and for the presence of serum hepatitis B virus
      surface antigen. None
      of the
      HCV-infected patients were receiving interferon
      therapy at the time of
      assessment.

      Two control groups were included in the study. One
      group consisted of
      40
      patients with at least one chronic systemic illness
      (such as diabetes
      mellitus, hypertension, coronary artery disease). All
      such ``non-liver
      controls'' had normal liver tests. The second control
      group consisted
      of 31
      healthy veterans who were selected during a routine
      health screening
      fair and
      served as normal controls.


      RESULTS

      The mean (��SD) age of all of the patient populations
      included in the
      study
      was 51.9 �� 11.6 years. Healthy subjects were
      age-matched with
      HCV-infected
      patients and with those with dual HCV and alcoholic
      liver disease. The
      mean
      age of patients with non-liver systemic diseases was
      higher compared
      with the
      other study groups: healthy subjects (46 �� 12.8
      years; p < 0.001),
      HCV-infected group (51.3 �� 10.7 years; p = 0.07), and
      patients with
      dual
      liver disease (45.8 �� 4.9 years; p = 0.03). There
      were no significant
      differences in the gender or racial compositions of
      the study groups.

      As expected, liver tests showed greater derangement in
      all of the three
      patient groups with liver disease compared with
      non-liver controls.
      Serum
      aminotransferase (alanine transaminase and aspartate
      transaminase)
      values
      were significantly
      higher in chronic HCV infection with or without
      chronic alcohol abuse
      compared with non-liver controls. In patients with
      alcoholic liver
      disease,
      serum aspartate transaminase values were higher than
      alanine
      transaminase
      levels, and these were
      significantly greater than non-liver controls.
      Similarly, serum albumin
      was
      significantly lower in all patient groups with liver
      disease compared
      with
      non-liver controls. However, the prothrombin time
      showed no significant
      difference between
      patients with liver disease and the non-liver
      controls.

      Fatigue Assessment Instrument

      The results of the 29-item Fatigue Assessment
      Instrument are shown in
      Table
      2. The total fatigue scores were significantly higher
      in all patient
      groups
      compared with healthy subjects (p < 0.005). However,
      there was no
      significant
      difference in
      the total fatigue scores between patients with
      different liver diseases
      (chronic HCV infection, dual HCV and alcoholic liver
      disease, and
      alcoholic
      liver disease alone) and subjects with non-liver
      systemic disorders.
      Similarly, there were no significant differences in
      the total fatigue
      scores
      among the various liver diseases.

      Analysis of different aspects of fatigue provided
      interesting results.
      The
      impact of fatigue on the individual in the form of
      interference with
      physical
      activity or mental concentration was significantly
      greater in patients
      with
      HCV infection compared with the other study groups;
      the difference
      reached
      statistical significance when compared with patients
      with non-liver
      disorders
      and healthy individuals (p < 0.05). Moreover, the
      physical and mental
      effects
      of fatigue, such as worsening lethargy and reduction
      in motivation,
      were also
      increased in HCV-infected individuals; the difference
      was statistically
      significant when compared with healthy subjects (p <
      0.005), but not
      with the
      other study groups. Relief from fatigue (after rest
      and sleep) was less
      effective in the HCV-infected patients; the difference
      was
      statistically
      significant when compared with healthy subjects and
      the non-liver
      control
      group, but not with other liver diseases.

      Sickness Impact Profile

      The results of the 65-item Sickness Impact Profile are
      shown in Table
      3. All
      parameters of the Sickness Impact Profile were in the
      four patient
      groups
      compared with healthy subjects. In general, patients
      with liver disease
      showed greater
      abnormalities compared with the patients with
      non-liver systemic
      disorders.
      The most significant difference was observed with
      respect to
      depression, in
      which the scores were significantly greater in
      patients with chronic
      HCV
      infection (19.5 ��
      12.0; p = 0.004), dual liver disease (20.9 �� 13.1; p
      < 0.001), and
      alcoholic
      liver disease (19.2 �� 16.1; p = 0.017) than in the
      non-liver controls
      (10.8 ��
      11.0). However, there was no significant difference in
      the depression
      scores
      among the three chronic liver disease groups.

      Feelings of anger and hostility were significantly
      greater in patients
      with
      chronic HCV infection, whether they were completely
      abstinent (17.0 ��
      10.0; p
      = 0.007) or indulging in heavy alcohol use (17.1 ��
      9.8; p < 0.001),
      compared
      with patients with non-liver chronic systemic
      illnesses (10.0 �� 9.5).
      Patients with alcoholic liver disease had scores for
      anger and
      hostility that
      were similar to non-liver controls, which were lower
      than scores in
      patients
      with HCV infection, but the difference failed to reach
      statistical
      significance. Poor energy level and fatigue were
      higher in HCV-infected
      subjects compared with the other liver disease groups;
      this difference
      was
      statistically significant compared with patients with
      non-liver
      systemic
      diseases (p < 0.01). Thus, the total of the negative
      Sickness Impact
      Profile
      parameters (depression, tension, anger, and fatigue)
      were significantly
      greater in the HCV-infected groups (both abstinent and
      current alcohol
      users)
      than in the other study groups. By contrast, positive
      parameters, such
      as
      vigor and vitality, were significantly reduced in all
      patient groups
      compared
      with healthy subjects, but there was no difference
      between the patients
      groups.

      DISCUSSION

      Assessment of fatigue and its impact on the quality of
      life in HCV
      infection
      has produced conflicting results. In a study on
      asymptomatic blood
      donors,
      HCV-infected individuals had a benign infection and
      most did not suffer
      any
      serious consequences as a result of this illness.15 In
      another study,
      conducted at the National Institutes of Health, 108
      patients with
      HCV-related
      liver disease were given a self-administered
      questionnaire to assess
      the
      degree of disease-related symptoms.3 The results were
      compared with a
      similarly tested control group of 100 healthy blood
      donors without
      antibody
      to HCV. There was no difference between the two groups
      with regard to
      the
      symptoms of hepatitis, and a similar proportion of
      healthy subjects and
      patients with HCV reported fatigue (70% and 62%,
      respectively).
      However,
      using specifically
      designed and validated instruments, several workers
      have found
      significantly
      greater disability in the quality of life in patients
      with chronic HCV
      compared with uninfected individuals.7���10,12,13

      An important aspect of assessing the impact of chronic
      HCV infection is
      determining whether the reduction in the patient's
      quality of life is
      caused
      by the HCV or the comorbidities associated with the
      illness. For
      example,
      patients with HCV
      frequently have history of alcohol and drug abuse and
      may be coinfected
      with
      hepatitis B virus. In one study, the investigators
      adjusted for some of
      these
      comorbidities,8 whereas another study excluded
      patients with a history
      of drug
      abuse from analysis.9 The results showed that despite
      exclusion of such
      confounding factors, patients with HCV infection had a
      greater
      reduction in
      their quality of life scores.

      Another potential source of conflict is the issue of
      whether the
      reduction in
      the quality of life is related to liver disease or to
      HCV infection. To
      assess this issue, some studies excluded patients with
      cirrhosis and
      still
      found a reduction in the quality of life scores.9,10
      The direct effect
      of HCV
      infection can be tested by assessing patients before
      and after
      antiviral
      therapy. Recent studies have shown that successful
      elimination of the
      virus
      is accompanied with improvement in quality of life
      scores; the extent
      of
      improvement was directly related to sustained
      virologic and biochemical
      responses to treatment. Conversely, nonresponders
      showed either a
      less-pronounced benefit or had a significant decline
      in quality of
      life.

      In the current study, we went a step further. We
      compared fatigue
      scores in
      patients with HCV infection, alcoholic liver disease,
      and dual alcohol
      and
      HCV infection, which allowed us to determine the
      impact of different
      liver
      diseases that were clinically and biochemically
      well-compensated. We
      also
      included two control groups: patients with non-liver
      chronic systemic
      disorders (such as diabetes mellitus and coronary
      artery disease) and
      healthy
      veterans. The healthy controls were age-matched with
      patients with
      liver
      disease but were otherwise selected at random.
      Assessment of this group
      permitted us to compare patients with liver disease
      with a healthy
      population
      of veterans who had a similar service background and
      who had been
      exposed to
      similar combat experiences.

      Patients with HCV infection had greater total fatigue
      scores than all
      the
      other study groups, although the differences reached
      statistical
      significance
      only against the healthy control subjects. Fatigue
      scores were higher
      in HCV
      infection than in
      alcoholic liver disease and in patients with dual
      alcohol and HCV
      infection.
      Subgroup analysis showed that all aspects of fatigue,
      such as the
      impact and
      consequence of fatigue on the individuals' general
      health, the response
      to
      relieving factors
      (such as rest and sleep), and the effect of triggering
      influences (such
      as
      stress and work), were worse in patients with HCV than
      in the other
      patient
      groups. These findings indicate that HCV infection is
      associated with
      greater
      fatigue despite a
      similar severity in the underlying liver disease.
      Patients with
      non-liver
      systemic disorders also had significantly higher
      fatigue scores than
      healthy
      subjects, but in general these were lower than those
      seen in the three
      liver
      disease groups.

      The pathogenesis of fatigue is unclear, and several
      factors have been
      incriminated. Excessive production of cytokines such
      as interferon,
      interleukin-1, and tumor necrosis factor- may be
      involved in the
      development
      of chronic fatigue syndromes.16���18 Some studies have
      noted elevated
      cytokine
      levels in patients with chronic liver disease,19
      whereas others have
      found no
      causal link between cytokines and fatigue.20���22 The
      most common risk
      factor
      for HCV infection worldwide
      is injected drug use; in this population, the
      seropositivity rate of
      HCV is
      nearly 80% in the United States.23,24 Patients with
      chronic alcoholism
      also
      have a high prevalence of HCV infection, with rates
      varying from 15% to
      over
      50%.25���29 It has
      been suggested that the reduction in quality of life
      scores found in
      HCV
      infection may be attributable to factors such as
      psychiatric
      disturbances
      associated with previous or current substance abuse.30
      To examine this
      issue,
      we used the Sickness Impact Profile, an instrument
      that assesses both
      negative psychologic attributes, such as depression,
      tension, anxiety,
      and
      anger, as well as positive ones, such as vigor. All of
      the patient
      groups had
      higher total negative scores and lower scores for
      vigor than the
      healthy
      subjects. In general, most of the individual
      components of the Sickness
      Impact Profile showed greater derangement in liver
      disease compared
      with
      non-liver systemic disorders, with HCV-infected
      patients showing the
      highest
      negative scores compared with all other study subjects
      (Table 3). These
      observations suggest
      that psychologic abnormalities may have a direct role
      in the
      pathogenesis of
      fatigue in HCV infection.

      In summary, the current study has shown that compared
      with healthy
      individuals, both fatigue and psychologic disturbances
      are more severe
      in
      patients with chronic illnesses and that the most
      severe abnormalities
      occur
      in HCV infection. We believe the lack of statistical
      significance in
      some of
      the observations is related to the relatively small
      number of
      individuals
      included in the different groups, a defect that can be
      remedied by
      performing
      large, multicenter studies. Our results show that the
      fatigue
      experienced by
      HCV-infected patients is not only more severe but also
      is more
      intransigent,
      responding less well to relieving factors such as rest
      and sleep.
      Moreover,
      patients with HCV infection appear more depressed and
      exhibit greater
      feelings of anger and hostility. Our findings have
      important
      therapeutic
      implications because effective treatment of the
      psychologic
      disturbances may
      improve patients' fatigue and, thus, may have a
      beneficial impact on
      the
      quality of life of patients with HCV.


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