Severe neutropenia and post-hepatitis C cirrhosis treatment: is interferon dose adaptation at once necessary?

Renou, Christophe; Harafa, Abdelouahid; Bouabdallah, Réda; Dematteï, Chritophe; Cummins, Catherine; Rifflet, H; Müller, P; Ville, Eric; Bertrand, Jean-Jacques; Benderitter, T; Halfon, Philippe

doi:10.1111/j.1572-0241.2002.05716.x

Cited by 18 publications

(13 citation statements)

References 14 publications

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“…Through sponsor contact, we received data from a clinical trial evaluating the efficacy of combination therapy with Peg‐IFN plus ribavirin [9]. Overall, 19 unique studies addressed effectiveness [9,27,28,31,32,35,36,38–41] and safety [24–26,29,30,33,34,37]. There was one RCT [32], three retrospective cohort studies [27–29] and 15 case series [9,24–26,30,31,33–41].…”

Section: Systematic Review Resultsmentioning

confidence: 99%

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Granulocyte colony‐stimulating factor for hepatitis C therapy‐associated neutropenia: systematic review and economic evaluation

Tandon¹,

Doucette

Fassbender

et al. 2011

Journal of Viral Hepatitis

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Hepatitis C virus (HCV) treatment requires maximal adherence to pegylated interferon (Peg-IFN) and ribavirin to achieve a sustained virologic response (SVR). Neutropenia is the most common cause for Peg-IFN dose reduction. Our objectives were to evaluate the effectiveness, safety and cost-effectiveness of granulocyte colony-stimulating factor (G-CSF) versus Peg-IFN dose reduction for HCV therapy-associated neutropenia in treatment naïve adults. We conducted a systematic review to identify controlled trials and observational studies. Study selection, quality assessment and data extraction were completed independently by two investigators. Cost-effectiveness and cost-utility analyses compared G-CSF with dose reduction. Nineteen studies were included. In one trial, the SVR for those receiving G-CSF was 54.5% (95% CI: 34.7-73.1) compared with 26.3% (95% CI: 11.8-48.8) for dose reduction. The remaining studies were case series or retrospective cohorts and provided weak evidence for the relationship between SVR and G-CSF. The risk of adverse events, including infection, associated with G-CSF was low (13.1%; 95% CI: 8.0-20.8) and clinically insignificant. G-CSF had an incremental cost-effectiveness ratio of $41,701 per SVR achieved in genotype 1, and $16,115 per SVR achieved in genotype 2 or 3. Estimates were robust under a variety of resource and intervention scenarios. While administration of G-CSF may enable patients to remain on or resume optimal HCV therapy, there was weak evidence that this improves the likelihood of SVR compared with dose reduction. Adverse effects of G-CSF are mild. The economic evaluation was inconclusive.

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Section: Systematic Review Resultsmentioning

confidence: 99%

“…Hepatitis C virus (HCV) therapy varied across studies (Table 1). The definition of neutropenia ranged from neutrophil count <0.75 × 10 9 /L [9,24–26,30–32,34,36,37] to <1.0 × 10 9 /L [27–29,33,41]. In two studies, neutropenia was defined as a white blood cell count <3000/μL [38] or <2000/nL [40].…”

Section: Systematic Review Resultsmentioning

confidence: 99%

Granulocyte colony‐stimulating factor for hepatitis C therapy‐associated neutropenia: systematic review and economic evaluation

Tandon¹,

Doucette

Fassbender

et al. 2011

Journal of Viral Hepatitis

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“…[60] Another study demonstrated that infections neither correlate with the nadir of neutrophil count (<1,000 or > 750/mm 3 ) nor with the magnitude of neutrophil count fall from the baseline. [59] This is in contrast to the observations made in immunodeficient cirrhotics,[61] HIV carriers[62] and liver transplant patients,[63] in whom prolonged neutropenia has been associated with the development of bacterial infections warranting the cessation of antiviral therapy. The frequency of development of superadded bacterial infection secondary to neutropenia appears to be lower in the black population.…”

Section: Erythropoietinmentioning

confidence: 88%

“…[5859] Whether or not neutropenia increases the risk of infection is also debatable. One study showed an average fall of 34% in the neutrophil count with no documented or suspected ensuing bacterial infection.…”

Section: Erythropoietinmentioning

confidence: 99%

Role of hematopoietic growth factors as adjuncts in the treatment of chronic hepatitis C patients

Danish¹,

Koul²,

Subhani³

et al. 2008

Saudi J Gastroenterol

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Drug-induced hematotoxicity is the most common reason for reducing the dose or withdrawing ribavirin (RBV) and interferon (IFN) therapy in chronic hepatitis C, which leads to the elimination of a possible cure for the patient. Traditionally, severe anemia and neutropenia have been considered as absolute contraindications to start antiviral therapy. This has not however, been the case since the advent of adjunct therapy with hematopoietic growth factors (erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF)). Some recent landmark studies have used this adjunct therapy to help avoid antiviral dose reductions. Although the addition of this adjunct therapy has been shown to significantly increase the overall cost of the treatment, this extra cost is worth bearing if the infection is cured at the end of the day. Although more studies are needed to refine the true indications of this adjunct therapy, determine the best dose regimen, quantify the average extra cost and determine whether or not the addition of this therapy increases the sustained virological response rates achieved, the initial reports are encouraging. Therefore, although not recommended on a routine basis, some selected patients may be given the benefits of these factors. This article reviews the current literature on this subject and makes a few recommendations to help develop local guidelines.

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“…However, earlier studies in patients with chronic hepatitis C have not correlated interferon-induced neutropenia with the occurrence of bacterial infections. Renou et al [24] studied interferoninduced neutropenia in 11 patients with compensated cirrhosis, four of whom developed ANCs less than 750 cells/mm 3 . The ANC increased in all patients after a period of 21 ± 5 days without dose reduction or G-CSF administration.…”

Section: Recent Advancesmentioning

confidence: 98%

Management of hematologic side effects: Impact on compliance and efficacy

Ahmed¹,

Jacobson

2005

Curr hepatitis rep

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Severe neutropenia and post-hepatitis C cirrhosis treatment: is interferon dose adaptation at once necessary?

Cited by 18 publications

References 14 publications

Granulocyte colony‐stimulating factor for hepatitis C therapy‐associated neutropenia: systematic review and economic evaluation

Granulocyte colony‐stimulating factor for hepatitis C therapy‐associated neutropenia: systematic review and economic evaluation

Role of hematopoietic growth factors as adjuncts in the treatment of chronic hepatitis C patients

Management of hematologic side effects: Impact on compliance and efficacy

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