Granulocyte colony‐stimulating factor dosing in pegylated interferon alpha‐induced neutropenia and its impact on outcome of anti‐HCV therapy*

Abstract

Many patients with chronic hepatitis C (HCV) infection undergoing treatment with pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin develop neutropenia requiring dose reduction or granulocyte colony-stimulating factor (G-CSF) supplement. We analysed the database of patients who completed treatment for chronic HCV infection between 2003 and 2006. Patients with absolute neutrophil counts below 1000 cells/microL were initiated on G-CSF (G-CSF group) while a matching group of patients who received anti-HCV treatment without developing neutropenia were used as a control group (non-G-CSF group). Patients on the G-CSF arm were divided into two subgroups based on the timing of G-CSF administration relative to PEG-IFN-alpha administration. Of the 163 patients with HCV infection, 30 patients received G-CSF, most of who were maintained on 300 microg of G-CSF once a week. Administration of G-CSF 2 days before or after each dose of PEG-IFN-alpha did not make a significant difference in the neutrophil counts. In the G-CSF arm, 23 of 30 patients (77%) had undetectable end-of-treatment viral response which was comparable with 27 of 30 in the control group (90%; P = 0.17). There was no statistically significant difference in the sustained viral response between the two groups (61%vs 76%, P = 0.18). In most patients PEG-IFN-alpha induced neutropenia improved with a once-a-week dose of G-CSF with a comparable virological outcome. Timing of G-CSF administration did not make any significant impact on the patient's neutrophil counts but was better tolerated when given 2 days apart from PEG-IFN-alpha.

Reduction in Neutrophil Count During Hepatitis C Treatment: Drug Toxicity or Predictor of Good Response?

“…In our study, two of four patients in whom peginterferon dose was reduced before 12th week of treatment suffered a relapse after stopping peginterferon and ribavirin. Unfortunately, the use of granulocyte-colony-stimulating factors has shown contradictory results [13,14]. New studies are needed to evaluate the safety and efficacy of lowering neutrophil thresholds for reducing the dose of peginterferon.…”

Acute septic shock during pegylated-interferon and ribavirin therapy in a patient with chronic hepatitis C who underwent aortic graft replacement

“…Therefore, guidelines for use of G-CSF for neutropenia during IFN therapy remain unclear. In addition, the use of G-CSF has not made a significant impact upon the virological outcome in IFN therapy [11]. In the present case, we did not use G-CSF because no significant deterioration of neutropenia was observed, and the patient did not show any sign of infection until she complained of sudden high fever.…”

“…Many clinicians have used granulocyte-colony stimulating factor (G-CSF) to help maintain ANC values during IFN therapy [10,11]. Unfortunately, three large studies failed to determine a specific ANC value to trigger supportive treatment [8,12,13].…”

Optimizing peginterferon and ribavirin administration in difficult-to-treat patient populations

“…However, administration of granulocyte colony-stimulating factor (G-CSF), 300 μg/wk, may not necessarily translate to better SVR rates [14]. As the literature expands on the effi cacy of the routine use of hematologic growth factors to treat HCV combination therapy-induced hematologic abnormalities, the role of growth factors in optimizing HCV treatment will be better defi ned.…”