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The use of EPO for HCV treatment associated anemia

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    NATAP - www.natap.org Anemia in the Treatment of Hepatitis C Virus Infection the use of EPO for HCV treatment associated anemia Clinical Infectious Diseases
    Message 1 of 1 , Dec 3, 2003
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      NATAP - www.natap.org

      Anemia in the Treatment of Hepatitis C Virus Infection

      the use of EPO for HCV treatment associated anemia

      Clinical Infectious Diseases 2003;37:S315-S322

      Mark S. Sulkowski
      Center for Viral Hepatitis, Johns Hopkins University, Baltimore,
      Maryland

      ABSTRACT. Hepatitis C virus (HCV) infection is a significant
      worldwide
      health
      care problem. Nearly one-third of all patients infected with human
      immunodeficiency virus (HIV) are coinfected with HCV.

      Compared with HIV-monoinfected persons, coinfected individuals
      experience
      more rapid progression of fibrosis and higher incidence of cirrhosis
      and death as
      a result of liver disease.

      Treatment for HCV infection includes ribavirin (RBV) plus interferon
      alfa
      (IFN-) or pegylated IFN, a combination treatment associated with
      anemia
      that may
      require RBV dose reduction or discontinuation. IFN-RBV associated
      anemia is
      more profound among coinfected patients, who have a high prevalence
      of
      pretreatment anemia and may also be taking other medications causing
      anemia.

      Epoetin alfa administration to HCV-infected patients with
      IFN-RBVrelated
      anemia can significantly increase hemoglobin levels and maintain
      significantly
      higher RBV doses compared with patients treated with RBV dose
      reduction
      alone.
      Higher RBV doses and adherence to HCV therapy have been associated
      with
      higher
      sustained virologic response (SVR) rates. Maintenance of RBV dose
      with
      epoetin
      alfa may improve adherence, thereby affecting SVR.

      EPIDEMIOLOGY OF HCV INFECTION

      With nearly 4 million people chronically infected with hepatitis C
      virus
      (HCV) in the United States, the health care burden resulting from HCV

      infection is
      likely to increase substantially in the next 2 decades. This is
      primarily
      because 85% of patients with acute HCV infection will subsequently
      develop
      chronic infection, and an estimated 20%-30% of these will develop
      cirrhosis. Chronic
      infection may also lead to hepatocellular carcinoma and is now the
      most
      common indication for orthotopic liver transplantation in the United
      States. In
      addition, the aging of the chronically infected population is
      estimated
      to
      increase the number of patients with HCV-related liver decompensation

      and to
      increase mortality 4-fold by the year 2018 compared with current
      rates
      of
      decompensation and mortality.

      Of significant concern is the high prevalence of HIV and HCV
      coinfection,
      which likely results from the similar modes of transmission for the
      viruses,
      particularly in injection drug users and recipients of transfused
      blood
      products.
      A recent report noted that 16% of a heterogeneous population of
      HIV-infected
      patients were coinfected with HCV. The increasing significance of
      HCV-HIV
      coinfection is also related to dramatic reductions in morbidity and
      mortality among
      HIV-infected patients during the HAART era, resulting in the
      emergence
      of HCV
      as a common pathogen in this population. Relatively more severe HCV
      disease
      occurs in this setting, possibly from HIV infection altering the
      response of T
      cells to HCV antigens. For example, an imbalance of Th1 (low) and Th2

      (high)
      activation may lead to an ineffective immune response to HCV
      infection.
      Although the mechanism has not been fully elucidated, HIV-infected
      patients have an
      increased risk for HCV disease progression compared with those with
      HCV
      monoinfection, leading to higher rates of cirrhosis, liver failure,
      hepatocellular
      carcinoma, and mortality.

      TREATMENT OF HCV INFECTION

      The primary objective of HCV treatment is virus eradication, which is

      the
      most effective way to delay or prevent the histologic (i.e., hepatic
      fibrosis)
      and clinical (i.e., liver failure, liver cancer, death) consequences
      of
      chronic
      HCV infection. Currently, the most effective therapy for chronic HCV
      infection
      is once-weekly (q.w.) pegylated interferon (PEG-IFN)--2a or --2b in
      combination with ribavirin (RBV). In 2 large, randomized controlled
      trials, a sustained
      virologic response (SVR), defined as absence of HCV RNA in serum by
      PCR
      assay
      24 weeks after treatment discontinuation, was achieved in 54%-56% of
      patients
      receiving PEG-IFN/RBV for 48 weeks. On the basis of these data, the
      2002
      National Institutes of Health Consensus Panel on the Management of
      Hepatitis C
      recommended that HCV-infected patients, including those coinfected
      with
      HIV, be
      considered for treatment with PEG-IFNRBV combination therapy.

      Factors predictive of response to combination PEG-IFNRBV therapy

      Further analysis of individuals who achieved SVR in the 2 randomized
      trials
      of PEG-IFN/RBV indicates that the most important pretreatment factors

      to
      predict SVR include HCV genotype and quantitative serum HCV RNA level

      (i.e., HCV
      load). SVR rates of 42% and 46% were achieved in patients with HCV
      genotype 1,
      compared with rates of 76% and 82% in patients with HCV genotypes 2
      or
      3.
      Furthermore, SVR rates were substantially lower among persons with
      high
      HCV RNA
      levels, defined as > 2 x 106 copies/mL, compared with those with
      lower
      HCV RNA
      levels. In the study by Manns and colleagues, SVR was achieved in 42%

      and 78% of
      PEG-IFN--2b/RBVtreated patients with high and low HCV-RNA levels,
      respectively. Similarly, Fried et al. reported SVR rates of 53% and
      62%
      for
      PEG-IFN--2a/RBVtreated patients with high and low HCV RNA,
      respectively. Thus, patients
      infected with HCV genotype 1 and high HCV RNA levels represent the
      patient
      subgroup that is the most difficult to treat.

      In addition to virologic factors, baseline liver histology also
      appears
      to be
      associated with SVR. Patients with evidence of advanced fibrosis or
      cirrhosis
      generally have lower SVR rates compared with those with no or minimal

      fibrosis.

      Importance of maintaining adequate IFN and RBV doses

      In addition to baseline factors, treatment regimen and patient
      adherence to
      this regimen are important factors in determining SVR. Emerging data
      suggest
      that a key element of successful combination therapy with IFN-RBV is
      the ability
      of the patient to maintain adequate doses of both drugs throughout
      the
      designated treatment period. Recently, McHutchison et al.
      demonstrated
      that patients
      who received at least 80% of the total doses of both PEG-IFN--2b and
      RBV for
      at least 80% of the expected duration of therapy had an SVR of 63%,
      compared
      with an SVR of 52% for those who received <80% of the total doses of
      both drugs
      for at least 80% of the expected therapy duration (P = .04).

      Importance of maintaining adequate IFN and RBV doses

      In addition to baseline factors, treatment regimen and patient
      adherence to
      this regimen are important factors in determining SVR. Emerging data
      suggest
      that a key element of successful combination therapy with IFN-RBV is
      the ability
      of the patient to maintain adequate doses of both drugs throughout
      the
      designated treatment period. Recently, McHutchison et al.
      demonstrated
      that patients
      who received at least 80% of the total doses of both PEG-IFN--2b and
      RBV for
      at least 80% of the expected duration of therapy had an SVR of 63%,
      compared
      with an SVR of 52% for those who received <80% of the total doses of
      both drugs
      for at least 80% of the expected therapy duration (P = .04).

      The importance of RBV dose was also evident in a recent phase 3
      randomized,
      controlled trial evaluating the efficacy of 2 PEG-IFN--2bRBV dosing
      regimens
      (PEG-IFN--2b 1.5 g/kg weekly plus RBV 800 mg/d for 48 weeks [n = 511]

      or
      PEG-IFN--2b 1.5 g/kg weekly for the first 4 weeks followed by 0.5
      g/kg
      weekly for the
      next 44 weeks plus RBV 1000-1200 mg/d [n = 514]) with that of IFN--2b
      3
      million U sc 3 times weekly (t.i.w.) plus RBV 1000-1200 mg/d (n =
      505)
      for 48 weeks
      in HCV-infected patients. In this study, the doses of PEG-IFN--2b
      selected
      reflected their antiviral effect when used as monotherapy, whereas
      the
      lower
      800-mg/d RBV dose was selected because of concern that the higher
      PEG-IFN--2b
      dose might be associated with anemia that would exacerbate the
      dose-dependent
      anemia observed with RBV.

      Interestingly, patients receiving the higher-dose pegylated product
      demonstrated higher SVR rates compared with those receiving
      lower-dose
      PEG-IFN--2b or
      IFN--2b. However, further analysis of the PEG-IFN--2b and RBV doses
      received
      indicated that adequate doses of both drugs were important and
      significantly
      predicted SVR (OR, 1.7, P = .002 for high-dose vs. low-dose
      PEG-IFN--2b
      and P =
      .015 for RBV). Plotted as a continuous variable, the likelihood of
      SVR
      increased with increasing RBV dose (expressed as mg of RBV received
      per
      kg of body
      weight). Additional logistic regression analysis showed that observed

      SVR rates
      generally increased as RBV dose increased up to 13 mg/kg, which
      corresponds to
      an RBV dose of 1000 mg/d in a 70-kg person. According to this
      analysis,
      the
      most effective RBV dose range is 1115 mg/kg, which corresponds to
      daily
      doses of
      800-1400 mg, depending on body weight. Further analysis showed that
      the
      SVR
      rate was higher in all study groups when the RBV dose was >10.6
      mg/kg;
      patients
      receiving higher-dose PEG-IFN--2b plus RBV doses >10.6 mg/kg had an
      overall
      SVR of 61%, compared with an SVR of 50% for those receiving the same
      PEG-IFN--2b dose but RBV doses 10.6 mg/kg.

      (Editorial note from Jules Levin: The use of RBV weight based dosing
      of
      800-1400 mg/day in combination with PegIntron was approved by
      regulatory
      authorities in Europe for use along with PegIntron, but it is not
      approved in the USA.
      The analysis of benefit presented to the FDA by Schering Plough from
      the study
      was retrospective. The FDA did not approve 800-1400 mg weight based
      dosing
      with PegIntron. Particularly in question was whether the study data
      supported the
      use of 1400 mg/day. The FDA recommended that Schering conduct a
      prospective
      study. The WIN-R Study is ongoing and examining prospectively RBV
      weight based
      dosing with PegIntron, and data on RBV weight based dosing has not
      yet
      been
      presented. In Pegasys/RBV studies, the use of 1000-1200 or 800 mg/day

      of RBV
      was prospectively studied and FDA approved. In HCV/HIV coinfection,
      it
      appears
      that higher dosing of RBV may be more difficult to tolerate, than in
      HCV
      monoinfection, One can initiate therapy with 1200mg and reduce dose
      if
      intolerable,
      but 1400mg/day is quite a lot).

      In addition, the significance of adequate RBV dose in patients with
      HCV
      genotype 1 was prospectively demonstrated in a multicenter,
      double-blind,
      randomized controlled trial conducted by Hadziyannis and colleagues
      among previously
      untreated persons chronically infected with hepatitis C. Study
      participants (N =
      1284) were randomized to 1 of 4 treatment groups comparing 2 RBV
      dosing
      schemes (800 mg/d vs. 1000-1200 mg/d) and 2 treatment durations (24
      weeks vs. 48
      weeks). Study results showed that, among persons infected with HCV
      genotype 1,
      the SVR rate was significantly higher for those treated with
      high-dose
      RBV
      (1000-1200 mg/d; SVR, 51%) for 48 weeks, compared with those treated
      with low-dose
      RBV (800 mg/d; SVR, 40%) for 48 weeks (P = .01). Conversely, among
      patients
      infected with HCV genotype 2 or 3, no difference in SVR rate was
      observed
      between low-dose and high-dose RBV treatment groups for 24 or 48
      weeks.

      Thus, these data, derived from large, randomized clinical trials,
      indicate
      that RBV dose and patient adherence are important factors in
      achieving
      SVR,
      particularly among "difficult-to-treat" patients, such as those
      infected with HCV
      genotype 1 and those with high baseline levels of HCV RNA. However,
      in
      all
      studies, the major, and sometimes dose-limiting, toxicity of
      PEG-IFNRBV
      was a
      dose-dependent hemolytic anemia.

      Hepatitis C in the HIV-infected patient

      Before the advent of HAART, clinicians caring for HIV-infected
      patients
      focused their attention on preventing traditional opportunistic
      infections and
      delaying progression of HIV disease to AIDS/death. In keeping with
      that
      strategy,
      chronic HCV infection that was presumed to be indolent in many
      patients
      was
      often not treated. However, in the era of HAART, HCV infection has
      emerged as a
      major cause of morbidity and mortality among HIV-infected patients.
      Consequently, HIV care providers have focused increasing attention on

      HCV treatment,
      with renewed research efforts to determine the most safe and
      effective
      regimen in
      this population.

      Although studies are currently under way, there are few published
      data
      addressing the safety and efficacy of IFN-a or PEG-IFN-a and RBV
      therapy in
      HIV-infected patients. Several retrospective treatment series suggest

      that IFN-RBV is
      reasonably well tolerated and may lead to persistent HCV clearance
      among some
      HIV-infected patients. In addition, preliminary data from ongoing
      clinical
      trials have recently been presented. Kostman and coworkers treated
      110
      HIV-HCV
      coinfected patients with IFN--2b plus RBV or placebo. After 12 weeks
      of
      therapy,
      HCV RNA was undetectable in 23% of patients receiving combination
      therapy,
      compared with 5% of those receiving monotherapy. Although SVR data
      are
      not yet
      available, the safety profile was similar in both treatment groups,
      with 18%
      and 23% of patients discontinuing therapy as a result of adverse
      events
      in the
      placebo and RBV groups, respectively.

      More recently, Chung and colleagues presented preliminary data from
      an
      ongoing AIDS Clinical Trials Group study, which randomized 134
      coinfected adults to
      standard IFN--2a 6 million U t.i.w. for 12 weeks followed by 3
      million
      U for
      36 weeks or PEG-IFN--2a 180 g weekly; both groups received RBV 600 mg

      daily
      with a possible dose escalation to 1000 mg daily (if tolerated). The
      majority of
      patients were white (48%) or black (34%), were male (82%), had a
      history of
      intravenous drug use (64%), and were infected with HCV genotype 1
      (83%); 10% had
      cirrhosis. The median age was 45 years. At study entry, 90% were
      receiving
      antiretroviral therapy and 59% had undetectable HIV RNA levels. The
      mean CD4
      cell count was 452/mm3. At week 24 of therapy, HCV RNA was
      undetectable
      (<60
      IU/mL) in 15% and 44% of standard and PEG-IFN plus RBV groups,
      respectively. Among
      persons with genotype 1 infection, HCV RNA suppression was observed
      in
      7% and
      33% of standard and PEG-IFN recipients, respectively (P = .0014).
      Among
      those
      with HCV genotypes other than genotype 1, HCV RNA suppression was
      observed in
      40% and 80% of standard and PEG-IFN recipients, respectively (P =
      .06).

      Histologic response at week 24 of therapy (defined as 2-point
      reduction
      in
      histological activity index score) was observed in 40% and 26% of
      standard and
      PEG-IFN virologic nonresponders, respectively. AIDS Clinical Trials
      Group grade
      4 adverse events were observed more frequently among PEG-IFN (n = 17)

      than
      among standard IFN (n = 4) recipients. However, premature treatment
      discontinuation was similar in both groups (12%). No adverse effect
      on
      control of HIV
      replication was observed. Absolute CD4 cell count decreased and CD4
      cell
      percentage increased in both treatment groups (PEG-IFN: -194
      cells/mm3,
      +3.5%; standard
      IFN: -112 cells/mm3, +2.5%), suggesting no significant impact on
      immune
      status. Multivariate logistic regression analysis of HCV genotype
      found
      week-24 HCV
      response was independently associated with PEG-IFN (OR, 0.0004),
      white
      race
      (0.016), Karnofsky Performance Status score of 100% at baseline, and
      fibrosis
      score 02 (0.021). These preliminary data suggest that PEG-IFN/RBV may

      produce
      virologic and/or histologic response in HIV-HCV coinfected patients,
      although
      SVR data are not yet available.

      Although adverse effects are common with IFN-RBV, anemia is of
      particular
      concern in patients coinfected with HCV and HIV who receive
      combination
      IFN-RBV
      therapy, because these patients are already at risk for anemia from
      HIV-related
      causes, including chronic disease, nutritional deficiencies,
      opportunistic
      infections, and concurrent therapies for HIV infection. In addition,
      RBV seems
      to cause more anemia in HIV-infected patients than in individuals not

      infected
      by HIV. Thus, the decision to treat coinfected patients with IFN-RBV
      must
      balance adverse effects of therapy, including anemia, with the
      potential benefit
      of effectively managing HCV infection.

      ANEMIA ASSOCIATED WITH IFN-RBV THERAPY

      The development of significant treatment-associated anemia is a
      concern
      in both HIV-infected and -uninfected persons receiving IFN-RBV.
      Decreased
      hemoglobin (Hb) levels have been reported in patients receiving both
      IFN and RBV,
      either alone or in combination. Of interest, 25%-30% of HCV-infected
      patients
      receiving IFN--2b alone demonstrated at least 2-g/dL decreases in Hb
      levels as
      a result of IFN-related bone marrow suppression, which limits RBC
      production.
      Furthermore, RBV monotherapy results in a dose-dependent,
      extravascular
      hemolytic anemia in most patients. Accordingly, patients treated with

      combination
      therapy are subject to RBV-related hemolytic anemia as well as
      IFN-related bone
      marrow suppression, which may impair the compensatory reticulocytosis

      that is
      an expected response to most hemolytic processes. Thus, many patients

      receiving IFN-RBV experience a "mixed anemia," with both hemolysis
      and
      bone morrow
      suppression developing simultaneously.

      The magnitude of treatment-associated anemia was further evaluated in
      a
      retrospective analysis of data from IFN--2bnaive (study 1, n = 192)
      and
      IFN--2bexperienced patients (study 2, n = 485). Enrolled patients had

      initial Hb levels
      >12 g/dL (women, n = 243) or >13 g/dL (men, n = 433) and were treated

      with
      standard IFN--2bRBV 10001200 mg/d; data from 208 women and 386 men
      were
      analyzed.
      In both studies, patients whose Hb levels decreased to <10 g/dL had
      RBV
      doses
      reduced to 600 mg/d. Overall, 54% of all patients had a 3-g/dL
      decrease
      in Hb
      level, and >27.7% of patients experienced Hb decreases of >25% of
      baseline
      levels. The incidence of Hb decreases 3 g/dL was higher in men (60%)
      than in
      women (44%) (RR, 1.4; 95% CI, 1.21.6). In addition, nearly 10% of men

      and 7% of
      women experienced an Hb decrease 5 g/dL. Thus, many patients
      receiving
      combination standard IFN-RBV therapy experience relatively
      significant
      declines in Hb
      levels.

      Similarly, anemia is a common complication of combination therapy
      with
      PEG-IFNRBV. In the study by Manns et al., patients receiving RBV
      doses
      >10.6 mg/kg
      had more-frequent dose modifications if they also received
      PEG-IFN--2b
      compared
      with standard IFN--2b (49% vs. 34%), most commonly as a result of
      neutropenia
      and anemia. However, treatment discontinuation was similar in the 2
      treatment
      groups (14% vs. 13%, respectively). In the study by Hadziyannis and
      colleagues, RBV discontinuation as a result of anemia was more common

      among patients
      treated for 48 weeks (18% and 19%) than among those treated for 24
      weeks (6% and
      7%). Thus, treatment-associated anemia among patients taking
      PEG-IFNRBV
      can
      necessitate RBV dose reduction or discontinuation, which may
      significantly
      decrease the probability of achieving an SVR.

      MANAGEMENT OF ANEMIA IN HCV-INFECTED PATIENTS

      Accordingly, strategies to address HCV treatmentassociated anemia are

      needed.
      The standard-of-care (SOC) management for patients who develop anemia

      during
      HCV therapy with IFN-RBV has been RBV dose reduction to 600 mg/d for
      Hb
      levels
      <10 g/dL and drug discontinuation when Hb levels drop to <8.5 g/dl.
      However,
      as discussed above, emerging data indicate that daily RBV doses <1000

      mg (for
      patients <75 kg) and 1200 mg (for patients 75 kg) are associated with

      lower
      SVR rates in HCV genotype 1infected patients. Consequently, to avoid
      RBV dose
      reduction and to improve symptoms related to Hb decreases, studies
      are
      needed to
      evaluate alternative approaches to the management of anemia in
      HCV-infected
      patients receiving IFN-RBV combination therapy.

      Recombinant human erythropoietin (epoetin alfa; PROCRIT; Ortho
      Biotech
      Products) is effective for the management of cancer-related anemia as

      well as for
      anemia in HIV-infected patients receiving antiretroviral therapy. On
      the basis
      of experience in these populations, epoetin alfa 40,000 U sc q.w. was

      administered in an open-label, prospective study of 18 HCV-infected
      patients receiving
      IFN-RBV who developed symptomatic anemia (Hb 10 g/dL or a decrease in

      Hb of 2
      g/dL from baseline) or a decrease in Hb accompanied by decreased
      exercise
      tolerance. Patients receiving IFN-RBV (n = 38) who did not meet these

      anemia
      criteria did not receive epoetin alfa and served as a comparison
      group.
      Patients
      were followed for a mean of 25.3 and 21.2 weeks, respectively. Among
      anemic
      patients, the mean Hb level had declined to 10.6 � 1.0 g/dL when
      epoetin alfa
      therapy was initiated. RBV doses were decreased before epoetin alfa
      initiation in
      8 patients and concurrently with epoetin alfa therapy in 5 patients.

      At study completion, mean Hb levels were 12.7 � 1.7 g/dL in the
      epoetin
      alfa
      group and 13.0 � 1.4 g/dL in the comparison group. In the anemic
      group,
      before
      initiation of epoetin alfa, the Hb decreased by a mean of 26.5% after

      IFN-RBV
      therapy administration; however, with the administration of epoetin
      alfa,
      nearly 75% of this Hb decrease was recovered by the end of follow-up.

      Interestingly, nearly 50% of the observed Hb decrease occurred during

      the first 2 weeks
      of RBV treatment, typically with symptoms of dyspnea and fatigue. In
      most
      patients, Hb recovery was rapid and often associated with an
      improvement in
      dyspnea.

      On the basis of these preliminary results, an open-label, randomized,

      parallel-group study involving 60 HCV monoinfected patients at 7
      centers in the
      United States was initiated. In this study, patients currently
      receiving IFN--2bRBV
      for HCV infection with Hb levels 12 g/dL were randomized to receive
      epoetin
      alfa 40,000 U sc q.w. for 16 weeks or SOC anemia management. The
      study
      objective was to determine the efficacy of epoetin alfa compared with

      SOC in
      correcting anemia and minimizing the need for anemia-related RBV dose

      reduction. At
      study entry, the mean Hb level was 11 g/dL for both groups. However,
      at
      the end
      of the 16-week study period, patients receiving epoetin alfa had a
      mean
      Hb
      level of 13.9 g/dL, compared with a mean Hb level of 11.3 g/dL for
      patients
      receiving SOC (P < .001). Similarly, mean daily RBV doses were 926
      mg/d
      and 782 mg/d
      for patients receiving epoetin alfa and SOC, respectively (P < .05).
      This
      represents a decrease from baseline RBV doses of 31 mg/d and 179 mg/d

      for
      patients receiving epoetin alfa and SOC, respectively (P < .05).
      Thus,
      epoetin alfa
      use was associated with an Hb increase of nearly 3 g/dL and
      maintenance
      of the
      intended RBV dose. Epoetin alfa therapy was well tolerated.

      Similarly, preliminary studies have evaluated the role of epoetin
      alfa
      in
      HIV-HCV coinfected patients who developed anemia during IFN-RBV
      therapy. In a
      small case series, 5 (23.8%) of 21 HIV-infected patients receiving
      IFN--2b plus
      RBV for concomitant HCV infection developed significant anemia. After
      a
      median
      of 4 weeks of treatment with epoetin alfa 40,000 U q.w., mean Hb
      levels
      increased from 10 to 12.7 g/dL, allowing continuation of combination
      therapy. Only 1
      of the 5 patients discontinued HCV treatment as a result of anemia,
      suggesting that anemia in HIV-HCV coinfection may also be managed
      with
      epoetin alfa;
      additional studies are ongoing in this population.

      SUMMARY

      Chronic HCV infection is an increasingly important cause of liver
      disease in
      the United States. Therapy with pegylated IFN-RBV can lead to SVR in
      54%-56%
      of treated patients. However, as a result of IFN-related bone marrow
      suppression and RBV-related hemolysis, anemia is a common
      complication
      of IFN-RBV
      therapy and may be associated with decreased quality of life and the
      need for RBV
      dose reduction. Recent data suggest that adherence to therapy and
      maintenance of
      the RBV dose are important factors in achieving SVR. Accordingly,
      epoetin
      alfa has been studied as a strategy to treat IFN-RBVrelated anemia.
      Preliminary
      data suggest that epoetin alfa can increase Hb level, improve quality

      of life,
      and decrease the need for RBV dose reduction in patients who develop
      IFN-RBV
      related anemia. Studies are currently under way to assess whether
      these
      improvements lead to enhanced patient adherence and increased
      hepatitis
      C response
      rates among HCV-infected patients with and without HIV coinfection.


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