Use of Epoetin (EPO) to Manage Anemia in Chronic Hepatitis C Patients Treated with Pegylated Interferon plus Ribavirin

Successful treatment of chronic hepatitis C with pegylated interferon plus ribavirin is often limited by anemia. An adequate amount of ribavirin reduces the risk of post-treatment HCV relapse, but the incidence of anemia rises with higher ribavirin doses. As reported in the August 2007 issue of Hepatology, researchers conducted a study to determine whether using erythropoietin, or epoetin alpha (EPO), with or without a higher dose of ribavirin, could enhance sustained virological response (SVR) rates. They randomized 150 treatment-naive patients (36% African-American) with chronic genotype 1 hepatitis C into 3 treatment groups:

Group 1: pegylated interferon alpha-2b (PegIntron) 1.5 mcg/kg/week + weight-based ribavirin 13.3 mg/kg/day (800-1400 mg/day);

Group 2: pegylated interferon + weight-based ribavirin + EPO (40,000 U/week);

Group 3: pegylated interferon + high-dose weight-based ribavirin (15.2 mg/kg/day; 1000-1600 mg/day) + EPO (40,000 U/week).

Pre-treatment total HCV-specific CD4 T-cell response was associated with sustained virological response (SVR) to pegylated interferon plus ribavirin.

In groups 2 and 3, EPO was started at the onset of therapy in order to maintain hemoglobin levels between 12 and 15 g/dL. When required, the ribavirin dose was reduced by 200-mg steps.

Results

A significantly smaller percentage of patients in Group 2 compared with Group 1 had a decline in hemoglobin to less than 10 g/dL (9% vs 34%; P < 0.05).

Fewer patients in Group 2 required ribavirin dose reduction (10% vs 40%) compared with Group 1 patients (P < 0.05).

Despite this, SVR rates were not significantly different in Group 1 and Group 2 (19% vs 29%).

However, the SVR rate was significantly greater (49%) in Group 3 (P < 0.05).

This resulted from a significantly lower HCV relapse rate: 8% in Group 3 vs 38% in Groups 1 and 2 (P < 0.05).

Conclusion

"We conclude that using EPO in all subjects at the initiation of pegylated interferon and ribavirin treatment will not enhance SVR given the same starting dose of ribavirin," the researchers stated. "In contrast, a higher starting dose of ribavirin was associated with a lower relapse rate and higher rate of SVR."

ML Shiffman, J Salvatore, S Hubbard, and others. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology 46(2): 371-379. August 2007.