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FW: NATAP: Alcohol/Depression/anemia-HCV care/treatment

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  • alleypat
    Alcohol & Depression: barriers to HCV treatmant Quality of life and cost-effectiveness of anti-HCV therapy in HIV-infected patients Journal of Hepatology
    Message 1 of 1 , Jan 31, 2006
      Alcohol & Depression: barriers to HCV treatmant

      Quality of life and cost-effectiveness of anti-HCV therapy in HIV-infected
      patients

      Journal of Hepatology
      Volume 44, Issue (Supplement 1), Pages S60-S64
      Maria Butia, John Wongb, Miguel Angel Casadoc, Rafael Estebana
      a Liver Unit, Hospital General Universitario Valle de Hebron, Paseo Valle
      hebron 117, Barcelona 08035, Spain
      b Clinical Decision Making, Tufts-New England Medical Center, Boston, MA,
      USA
      c Pharmacoeconomics & Outcomes Research Iberia, Madrid, Spain

      Quality of life studies in chronic hepatitis C using specific questionnaires
      have been performed in mono-infected patients; however, these studies have
      just begun in HIV-HCV co-infected patients. The questionnaires used in
      mono-infected patients are not well adapted for co-infected patients and
      need to be redesigned. Typically, co-infected patients have multiple
      symptoms that may be attributable to HIV, to HCV, to a combination of both
      diseases or even to side effects related to drug therapy. These patients
      usually need substitutive therapy to manage side effects related to HCV
      therapy, particularly anaemia, leukopenia and depression. There are no
      cost-effectiveness studies published on the current HCV standard therapy
      with pegylated interferon and ribavirin. However, there is some research on
      the old standard interferon and ribavirin, which shows that HCV therapy is
      cost-effective. Cost-effectiveness studies in co-infected patients will have
      to take into account variables that do not affect mono-infected patients,
      such as the different levels of CD4, the increase in the fibrosis
      progression rate and the use of other expensive drugs for the management of
      side effects. Currently, the literature does not provide adequate
      information on the effect of HCV infection on the quality of life of HIV-HCV
      co-infected patients or the most cost-effective HCV therapy.

      Article Outline
      o Abstract
      o 1. Introduction
      o 2. Limitations to HCV therapy
      o 3. Independent effect of alcohol
      o 4. Health-related quality of life and depression
      o 5. Cost-effectiveness of HCV therapy

      1. Introduction

      Co-infection with HIV and hepatitis C virus (HCV) is increasing and becoming
      recognized as a health problem in Europe. About 30% of HIV patients are
      co-infected with HCV, the majority of them being intravenous drug users
      [1-3]. HIV is a risk factor for HCV progression and accelerated HCV disease
      [4,5]. Currently, liver disease is a major cause of morbidity and mortality
      in co-infected patients [6-8]. Combination therapy with pegylated interferon
      and ribavirin is the best therapy for these patients, however, the sustained
      virologic response rate achieved is lower than mono-infected patients
      [9-13].

      2. Limitations to HCV therapy

      One of main concerns in the HCV-HIV population is to identify the proportion
      of patients eligible for therapy. There are few studies evaluating the
      suitability for HCV therapy with interferon and ribavirin in co-infected
      patients. In two prospective studies among 180 and 182 co-infected patients,
      respectively, only 30-33% of them were eligible for HCV treatment [14,15].
      The following factors are the main barriers: non-adherence with clinic
      visits, active psychiatric illness, active drug or alcohol use,
      decompensated liver disease, or medical illness. These barriers persisted
      despite ongoing education regarding the severity of HCV disease and the
      access to psychiatric and substance abuse programmes. However, the
      acceptance of anti-viral therapy for hepatitis C was similar between
      eligible persons with and without HIV [14,15]. These findings highlight the
      need to develop interventions to improve adherence and to manage substance
      abuse and other comorbidities in order to maximize the impact of interferon
      and ribavirin therapy on patients with chronic hepatitis C [16].

      Note from Jules Levin: anemia is another barrier to treatment in HCV,
      particularly for HCV/HIV coinfected patients. studies show Procrit can
      reduce fatigue associated with ribavirin, allow for higher dosing of
      ribavirin & higher ribavirin dosing is associated with higher rates of
      achieving Sustained Viral Responses, and lastly it was recently reported
      that Procrit is associated with achieving higher rates of Sustained Viral
      Response.

      3. Independent effect of alcohol

      The natural history of hepatitis C virus infection is altered by human
      immunodeficiency virus co-infection. Hepatic fibrosis and clinical features
      of hepatic dysfunction develop more rapidly in HIV/HCV co-infection than in
      HCV alone. Although HIV/HCV-co-infected patients may progress more rapidly
      to AIDS, other confounding variables include comorbidities, substance abuse,
      and social issues [17-19]. Alcohol consumption accelerates both HCV and HIV
      disease. It is thought that chronic alcohol abuse mediates liver damage as a
      result of increased production of free radicals and proinflammatory
      cytokines. In the setting of chronic HCV infection, alcohol ingestion has an
      additional effect of diminishing immune clearance and increasing viral
      burden to hasten the onset of cirrhosis and hepatocellular carcinoma [20].
      Clinical and experimental studies have demonstrated that excessive alcohol
      consumption can result in impairment of the immune system, and can impact
      several immune functions including immune tolerance and host defense against
      opportunistic infections, and development of certain tumours. Although, the
      effects of ethanol on the immune system involve multiple factors, several
      studies implicate chronic activation of immune cells and impairment of
      thymus-derived lymphocytes (T lymphocytes). Helper CD4+ T lymphocytes are
      the central regulators of the immune system and depletion of these
      lymphocytes is a major contributing factor in ethanol-induced immune
      dysfunction and exacerbation of HIV and/or HCV pathogenesis. However, the
      mechanisms involved in the ethanol-induced CD4+ T cell depletion have only
      recently begun to be elucidated [21]. Thus, the synergistic effects of
      alcohol abuse and HIV greatly impact on the morbidity and mortality for
      patients with HCV co-infection. Ultimately, this cumulative disease process
      will require far more aggressive management with abstinence and counselling
      for alcohol abuse; highly active anti-retroviral therapy (HAART) for HIV
      infection and combination anti-viral therapy for HCV infection to stem the
      rapid progression to end stage liver disease.

      4. Health-related quality of life and depression

      Health-related quality of life (HRQOL) is increasingly recognized as an
      important measure for assessing the burden of chronic diseases. Studies
      suggest that HCV infection significantly reduces HRQOL, even in the absence
      of cirrhosis, and that successful treatment of HCV is associated with an
      improvement in HRQOL [22-26]. Results of initial studies involving
      HIV-infected patients suggest that HIV-infection is also associated with
      reduced HRQOL, with evidence that concurrent psychiatric conditions and
      illicit drug use significantly impair HRQOL for these patients [27-29].
      However, results of studies on the effects of CD4 lymphocyte count, HIV
      load, and HAART on HRQOL have been contradictory [27-31].

      The impact of HCV/HIV co-infection on HRQOL is unknown. Most available data
      have been limited to HCV infection, with information obtained largely from
      patients entering multicentre interferon treatment trials, a highly selected
      patient group. The impact of HIV and HCV co-infection has been evaluated in
      a large urban cohort of HIV/HCV co-infected patients. The HRQOL of
      co-infected patients was compared with that of urban patients infected with
      either HIV or HCV alone in a cross-sectional study comprising 136 HIV/HCV
      co-infected patients, 110 patients with only HCV infection, and 53 patients
      with only HIV infection [32]. HRQOL was assessed using the Hepatitis Quality
      of Life questionnaire, a survey that has been validated for patients with
      chronic HCV infection and includes the generic SF-36 survey, three
      additional generic scales, and two hepatitis-specific scales [33]. In this
      study, HRQOL was reduced in a similar way for patients infected with HCV
      alone, with HIV alone, or with HIV/HCV co-infection compared with a sample
      of the US population adjusted for age, sex, and race. The explanation for
      these data is unclear, but it could be due to the fact that HRQOL is a
      subjective evaluation of an individual's perception of their health and
      well-being [34]. In addition, these data may reflect different expectations
      of health in the three groups of patients, specifically in those infected
      with HIV alone, who although having more severe physical disease may also
      have a reduced expectation of health. Alternatively, patients with HIV
      infection may have access to additional support services that partly
      compensate for worsening in physical health. In co-infected patients, HRQOL
      was not affected by HCV co-infection, CD4 cell count, or HIV load, although
      non-use of HAART was associated with lower physical component scores.
      However, a stratified multivariate analysis of the interaction effects
      between co-infection and the variables associated with HRQOL suggested that,
      for HIV-infected patients, co-infection with HCV had a negative impact on
      mental component scores for patients with high Karnofsky scores and for
      those with a history of depression. All of these results illustrate the
      complexity of looking at HRQOL in HCV HIV co-infected patients, in which
      multiple related variables are associated with well-being. HIV-specific
      parameters, such as low CD4 cell count and high virus load, have previously
      been shown to adversely affect HRQOL in some studies of HIV-infected
      patients [30,31].

      Concurrent psychiatric conditions and injection drug use were also important
      predictors of HRQOL for patients with HIV infection. In addition, HIV
      co-infection may have a negative impact on mental component scores (MCS) for
      HCV-infected patients with concomitant depression. Some studies have
      suggested the importance of current or previous depression as independent
      predictors of diminished MCS in patients with HCV infection. Psychiatric
      illness, active intravenous drug use, and unemployment were independent
      predictors of diminished HRQOL scores in all patients, and non-use of HAART
      was associated with lower scores in patients with HIV infection.

      Approximately, 24% of mono-infected patients with chronic hepatitis C, even
      before HCV therapy, have symptoms of depression [35]. The etiopathogenic
      mechanisms of depression are unknown although it appears that it could be
      attributed to excessive asthenia or related to the long-term prognosis of
      the illness [36]. Although there is broad-based information on the
      neuropsychiatric disturbances derived from interferon therapy, there have
      been few studies that analyse these effects of therapy on co-infected
      HIV/HCV patients [37]. Some studies suggest that the incidence of depressive
      symptoms in patients with HIV/HCV co-infection treated with interferon is
      high at around 40%. This rate is higher than that described for
      mono-infected patients and this could possibly be related to the neurotoxic
      effect of HIV and secondary effects on the central nervous system of some
      anti-retrovirals [37]. In addition, there are other risk factors for
      depression among this population such as past history of intravenous drug
      use. The way that interferon produces depressive symptoms are speculative
      and are based on disturbances in the central adrenergic, serotonergic and
      the neuroendocrine systems and probably also related to tryptophan
      deficiency [38]. Most of the depressive symptoms were mild and improved with
      anti-depressant therapy. The majority of them appear during the first 12
      weeks of interferon therapy, and usually no reduction or discontinuation of
      interferon therapy is necessary [39]. Some studies have shown the high
      efficacy of a selective serotonin re-uptake inhibitor (SSRI) in the
      treatment of depressive symptoms associated with interferon therapy. In
      addition, SSRI are shown to be well tolerated and safe in these patients
      [39-41]. During the first weeks after initiating interferon therapy for
      HIV/HCV co-infection, close control of the psychiatric symptoms is
      recommended. Early treatment of these side effects with anti-depressants
      would help avoid early dropouts from interferon therapy. Given the high
      incidence of depressive symptoms in patients co-infected with HIV and HCV
      being treated with interferon, it is crucial that a correct evaluation of
      the patient is carried out before prescribing treatment and a strict
      monitoring of the secondary effects by a multidisciplinary team including
      infection specialists, psychiatrists and hepatologists [42]. In the presence
      of depressive symptoms after initiation of interferon, an adequate
      therapeutic approach would be to begin low-dosage SSRI on a rising scale
      until the desired response is obtained. Later, the same dosage should be
      maintained until interferon treatment is completed.

      5. Cost-effectiveness of HCV therapy

      The health and economic consequences of therapy of chronic hepatitis C has
      been widely analyzed in cost-effectiveness studies in mono-infected patients
      [43-47]. All of them showed that HCV therapy with interferon monotherapy or
      combination therapy with interferon and ribavirin are cost-effective
      [43-46]. Studies on cost-effectiveness of HCV therapy in co-infected
      patients are scarce. There is some research with interferon and ribavirin,
      showing that HCV therapy is cost-effective in this setting [47].
      Cost-effectiveness studies in co-infected patients have also to take into
      account some variables, which do not affect mono-infected patients, such as
      the different levels of CD4, the increase in the fibrosis progression rate
      and the use of other expensive drugs such as epoetin and filigastrim for the
      management of side effects. Preliminary data suggested that for co-infected
      patients with a mean CD4 cell count of 350cells/N<l and moderate disease,
      treatment with combination therapy using interferon or pegylated interferon
      and ribavirin increases quality-adjusted life expectancy and has a
      cost-effectiveness ratio comparable to other well-accepted clinical
      interventions [47,48]. As in mono-infected patients, combination therapy is
      more cost-effective in patients infected by genotype non-1 than in patients
      infected by genotype 1.

      Currently, the literature does not provide adequate definitive information
      on the effect of HCV infection on the quality of life of HIV-HCV co-infected
      patients and no specific recommendations for the most cost-effective HCV
      therapy in this setting can be given.


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