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

Abstract

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.

The role of eltrombopag in the management of hepatitis C virus-related thrombocytopenia

“…A pretreatment platelet count of <90,000/mm 3 is a relative contraindication to commencing PEG-IFN therapy 71. If the pretreatment platelet level is above this cut-off value, and thrombocytopenia develops following initiation of PEG-IFN therapy, one treatment option may be to continue PEG-IFN therapy but to reduce its dose (minimum effective dose is 1 μg/kg/week) if the platelet count is <30 × 10 9 /L, or to discontinue it if the platelet count is <20 × 10 9 /L 55,72. Reductions in the dosage schedule of PEG-IFN can compromise the success of the therapy.…”

“…71 If the pretreatment platelet level is above this cut-off value, and thrombocytopenia develops following initiation of PEG-IFN therapy, one treatment option may be to continue PEG-IFN therapy but to reduce its dose (minimum effective dose is 1 μg/kg/week) if the platelet count is <30 × 10 9 /L, or to discontinue it if the platelet count is <20 × 10 9 /L. 55 , 72 Reductions in the dosage schedule of PEG-IFN can compromise the success of the therapy. To help maintain an optimal dosage schedule, adjunct eltrombopag (or romiplostim) may be considered to counteract thrombocytopenia in a sustained manner.…”

Human platelets and their capacity of binding viruses: meaning and challenges?

“…Indirect evidence supports also the hypothesis of bone marrow suppression by HCV, partly mediated by a reduction of thrombopoetin (TPO) production due to liver cirrhosis and/or fibrosis [ 29 - 31 ]. However, in HCV infection, the virus itself or other mechanisms can also lead to low platelet counts [ 32 - 34 ]. Thrombocytopenia in HCV infection is complex and multiple mechanisms are involved.…”

Antiviral therapy in HCV-infected decompensated cirrhotics

“…Possible indications of EPO include a fall in Hb level by >4 g/dL, Hb levels of <8 g/dL, and patients developing symptoms and signs of anemia (palpitations, dyspnea, easy fatigability, pallor). [ 21 22 ]…”