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Anemia during Hepatitis C Treatment Predicts Sustained Response to Pegylated Interferon/ribavirin

Hepatitis C patients who develop anemia during treatment with pegylated interferon plus ribavirin are more likely to achieve a sustained virological response (SVR), according to data from the IDEAL trial published in the November 2010 issue of Gastroenterology. Both ribavirin dose reduction -- which did not decrease SVR -- and medications that stimulate red blood cell production may be used to manage anemia and help people stay on treatment, the study authors concluded. alt

Anemia is a common side effect of treatment for chronic hepatitis C virus (HCV) infection, due to red blood cell destruction (hemolytic anemia) caused by ribavirin and bone marrow suppression related to interferon.

Erythropoietin (Procrit) and other erythropoiesis-stimulating agents (ESAs) that boost red blood cell production may be used to manage anemia. Reducing the dose of ribavirin is also done to control anemia, but this may increase the risk of post-treatment relapse, and therefore decrease the likelihood of achieving sustained response.

Mark Sulkowski and fellow investigators looked at the relationship between treatment outcomes, anemia, and use of ribavirin dose reduction and ESAs among participants in the IDEAL trial.

As previously reported, IDEAL compared 180 mcg/week pegylated interferon afa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin versus 1.0 or 1.5 mcg/kg/week pegylated interferon alfa-2b (PegIntron) plus 800-1400 mg/day ribavirin in more than 3000 previously untreated genotype 1 chronic hepatitis C patients at 118 U.S. sites. Participants who received Pegasys had a higher end-of-treatment response rate, but those taking PegIntron had a lower relapse rate, so SVR rates ended up about the same.

IDEAL participants who developed anemia -- defined as a hemoglobin level < 10 g/dL -- first had their ribavirin dose reduced and then were permitted to use ESAs if this was not sufficient.

In the present analysis, investigators analyzed sustained response rates according to decreases in hemoglobin, anemia, and ESA use. A total of 3023 patients had their hemoglobin levels measured at least once during treatment.


  • 865 participants (28.6%) developed anemia during treatment.
  • 449 of these patients (51.9%) used ESAs, usually after ribavirin dose reduction.
  • Patients who developed anemia were significantly more likely to achieve sustained virological response.
  • SVR rates were associated with magnitude of hemoglobin decline:
    •  Drop of > 3 g/dL: SVR 43.7%;
    •  Drop of < 3 g/dL: 29.9%.
  • Participants who reduced their ribavirin dose were not significantly less likely to achieve SVR
  • Among patients with early-onset anemia (through week 8 of treatment), those who used ESAs had a significantly higher SVR rate than those who did not (45.0% vs 25.9%).
  • People with early anemia who used ESAs were also significantly less likely to discontinue treatment due to adverse events (12.6% vs 30.1%, respectively).
  • However, ESA use did not affect SVR or treatment discontinuation rates among patients who developed anemia after 8 weeks.

"Among HCV genotype 1-infected patients treated with [pegylated interferon/ribavirin], anemia was associated with higher rates of SVR," the study authors concluded.

"The effect of ESAs varied by time to anemia," they continued. "[P]atients with early-onset anemia had higher rates of SVR with ESA use, whereas no effect was observed in those with late-onset anemia."

Importantly, the likelihood of HCV relapse did not increase among patients who decreased their ribavirin dose, in constrast with some prior research.

These findings "firmly underscore the recommendation for [ribavirin] dose reduction as the primary strategy for management of treatment-related anemia," before using ESAs, the researchers wrote. They added that, "ESAs should not be used solely to avoid [ribavirin] dose reduction in anemic patients."

Investigator affiliations: Johns Hopkins University School of Medicine, Baltimore, MD; Bon Secours Health System, Liver Institute of Virginia, Newport News, VA; Beth Israel Liver Center, Boston, MA; University of Pennsylvania Health System, Philadelphia, PA; Mount Vernon Endoscopy Center, Alexandria, VA; University of Texas Southwestern Medical Center, Dallas, TX; Thomas Jefferson University, Philadelphia, PA; Brooke Army Medical Center, Fort Sam Houston, TX; Cedars-Sinai Medical Center, Los Angeles, CA; Schering-Plough Research Institute (now Merck & Co), Whitehouse Station, NJ; Duke Clinical Research Institute, Durham, NC.




MS Sulkowski, ML Shiffman, NH Afdhal, and others (IDEAL Study Team). Hepatitis C virus treatment-related anemia is associated with higher sustained virologic response rate. Gastroenterology 139(5): 1602-11 (Abstract). November 2010.

Other Source

Reuters Health. Anemia in treated-HCV patients bodes well for sustained virological response. December 12, 2010.