PubMed · 946894
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W H Crosby. 1976-06-21. Pica.. https://pubmed.ncbi.nlm.nih.gov/946894/
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Hematologic side effects (anemia, neutropenia, and thrombocytopenia) of combination therapy with pegylated (PEG)-interferon alfa and ribavirin are commonly encountered during antiviral therapy for chronic hepatitis C (HCV). An important consequence of these side effects is dose modification of PEG-interferon alfa, ribavirin, or both. Dose modification (including discontinuation) diminishes the efficacy of optimal treatment regimen for HCV and may have a negative impact on sustained virologic response. Additionally, fatigue associated with anemia may impair patients' quality of life. The clinical implications of neutropenia or thrombocytopenia are less clear than for anemia; nevertheless, severe infection and bleeding are uncommon. Dose adjustments effectively treat these hematologic side effects, but the resulting suboptimal dosing and potential impact on virologic response are major concerns. Recent attempts to maximize adherence to the optimal treatment regimen have used hematopoietic growth factors rather than dose adjustment to treat side effects. Research on growth factor support has focused on anemia and neutropenia. Epoetin alfa and darbepoetin alfa are erythropoietic growth factors that effectively increase hemoglobin while maintaining the optimal ribavirin dose and improving patients' quality of life. Preliminary work suggests that filgrastim, granulocyte colony stimulating factors, may be an effective treatment of interferon-induced neutropenia. Although this early work shows tremendous promise for managing hematologic side effects of combination therapy for HCV, and potentially enhancing adherence, further research is needed to clarify the efficacy, safety, and cost-effectiveness of growth factors in the management of patients with chronic HCV.
Pegylated (PEG)-interferon and ribavirin combination therapy are the standard of care for the treatment of chronic hepatitis C and are associated with a high rate of sustained virologic response. However, there is a high incidence of hematologic side effects with this therapeutic regimen. Hematologic side effects are particularly common; bone marrow suppression caused by interferon may result in neutropenia and thrombocytopenia. Ribavirin is directly toxic to red blood cells and is associated with hemolysis, which is usually dose-related but self-limited. Historically, the traditional management of hematologic side effects of interferon therapy has been dose reduction. However, recent studies have shown that response to therapy is strongly influenced by adherence to optimal doses of interferon and particularly ribavirin. Therefore, there is increasing emphasis on the use of growth factors such as filgrastim and erythropoietin to stimulate bone marrow production of erythrocytes and leukocytes to allow patients to receive the optimal doses of interferon and ribavirin. The incidence, magnitude, and possible mechanisms of hematologic complications associated with interferon and ribavirin are described in this review.
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