for Health Care Providers
Recombinant erythropoietin is FDA-approved for treatment of anemia in a variety of clinical situations, but is not approved for anemia associated with HCV therapy. Mean decreases in Hb in patients taking ribavirin are 2-3 g/dL, declines that often lead to symptoms of fatigue and shortness of breath. Options for managing HCV treatment-related anemia include ribavirin dose reduction, ribavirin dose discontinuation, and/or addition of an erythropoietic growth factor.
Ribavirin dose reductions to manage treatment-related anemia may reduce SVR, though the impact on SVR of ≤20% dose reduction is unclear. Therefore, maintaining ≥80% of the original ribavirin target dose, especially during the first 12 wk of therapy, is reasonable. Clearly, early discontinuation of ribavirin results in a significant reduction in SVR (31) .
The role of erythropoietin to limit ribavirin dose reduction or discontinuation has been explored as a strategy to overcome treatment-related anemia. Erythropoietin therapy appears to maintain ribavirin doses and improve quality of life in patients who develop anemia related to HCV therapy (75, 76) . However, the impact on SVR still remains to be determined.
Erythropoietin may be more beneficial in patients with bone marrow suppression from HIV infection or from exogenous immunosuppression following liver transplantation. In addition, erythropoietin may be given prior to HCV therapy to patients with mild anemia (Hb <11 g/dL) who might otherwise not tolerate ribavirin, particularly in those with advanced HCV disease. If erythropoietin is administered, the initial dose of epoetin alfa is 40,000 units subcutaneously once weekly (titrated up to 60,000 units subcutaneously once weekly) or darbepoetin alfa 200 mcg subcutaneously every 2 wk (titrated up to 300 mcg subcutaneously every 2 wk). Hemogloblin and hematocrit levels should be monitored at least every 2 to 4 wk. Based on the manufacturers' warning of risks for cardiovascular and thrombotic events, the dose should be reduced if the baseline Hb increases by >1 g/dL in any 2-wk period and if Hb levels exceed 12 g/dL (53, 77, 78) . For additional information, please refer to Recombinant Erythropoietin Criteria for Use for Hepatitis C Treatment-Related Anemia.
RECOMMENDATIONS FOR ERYTHROPOIETIN USE
1. Erythropoietin may be administered in patients with symptomatic anemia related to ribavirin therapy and/or to limit anemia-related ribavirin dose reductions or discontinuations, particularly in those who are cirrhotic, postliver transplantation, and HIV/HCV coinfected (I).
2. Erythropoietin may be given preemptively in patients with pretreatment anemia (Hb <11 g/dL) in order to facilitate ribavirin dosing, particularly in those with advanced HCV disease (III).
Granulocyte Colony Stimulating Factor (GCSF)
Moderate neutropenia is a common adverse effect of peginterferon alfa, resulting in ANC <750/mm3 in approximately 20% of those treated. Peginterferon alfa doses of <60% of the original dose appear to reduce SVR (31) . Limited data suggest that GCSF increases white blood cells and may permit administration of higher interferon doses in managing interferon-induced neutropenia in patients with HCV and/or undergoing liver transplantation (69, 79, 78, 80, 81) ; however, improvements in SVR have not been demonstrated. Furthermore, it is unclear whether the risk of infection is related to the degree of interferon-induced neutropenia (82) .
GCSF may be appropriate for patients who are cirrhotic, postliver transplant, or HIV/HCV coinfected with an ANC <500/mm3, particularly if neutropenia persists despite peginterferon alfa dose reduction. Typical dosing of GCSF is 300 mcg subcutaneously once to twice weekly; doses can be titrated to desired ANC >500/mm3 based on ANC nadir levels (69) .
RECOMMENDATIONS FOR GCSF USE
1. GCSF should not be given as primary therapy to prevent peginterferon alfa dose reductions (III).
2. GCSF may be administered in patients who are cirrhotic, postliver transplantation, or HIV/HCV coinfected with an ANC <500/mm3, particularly if neutropenia persists despite peginterferon alfa dose reduction (III).
As liver disease worsens, serum thrombopoietin levels decline (83) . Limited experience with thrombopoietin in HCV-infected patients on antiviral therapy suggests that platelet counts increased, although fluid retention, an adverse effect of thrombopoietin, was common (84) . Until additional safety and efficacy data are available, thrombopoietin cannot be recommended for patients on interferon therapy.