title: Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha.
abstract: Successful treatment of chronic HCV with peginterferon (PEGIFN) and ribavirin (RVN) is often limited by anemia. We performed the present study to determine if utilizing epoetin alpha (EPO) with or without a higher dose of RVN could enhance sustained virologic response (SVR). We randomized 150 treatment-naive patients with chronic HCV genotype 1 into 3 treatment groups: (1) PEGIFN alpha-2b (1.5 microg/kg/week) + weight-based RVN (WBR) 13.3 mg/kg/day (800 to 1400 mg/day); (2) PEGIFN alpha-2b + WBRVN + EPO (40,000 U/week); or (3) PEGIFN alpha-2b + higher dose WBR 15.2 mg/kg/day (1000 to 1600 mg/day) + EPO. We initiated EPO at the onset of therapy to maintain the hemoglobin between 12 and 15 g/dL. When required, we reduced RVN by 200-mg steps. African Americans compose 36% of the population. A significantly smaller percentage of group 2 patients had a decline in hemoglobin to less than 10 g/dL (9% versus 34%; P < 0.05) and required that the RVN dose be reduced (10% versus 40%; P < 0.05) compared to group 1 patients. Despite this, SVR was similar in these groups (19% to 29%). SVR was significantly greater (P < 0.05) in group 3 patients (49%). This resulted from a significant decline (P < 0.05) in relapse rate; only 8% versus 38% for groups 1 and 2.
  
  
  CONCLUSIONS
  We conclude that using EPO in all subjects at the initiation of PEGIFN and RVN treatment will not enhance SVR given the same starting dose of RVN. In contrast, a higher starting dose of RVN was associated with a lower relapse rate and higher rate of SVR.
authors.affiliation: Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA. mshiffma@vcu.edu
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Salvatore
authors.forename: Sarah
authors.initials: S
authors.lastname: Hubbard
authors.forename: Angie
authors.initials: A
authors.lastname: Price
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D004921:Erythropoietin; D011092:Polyethylene Glycols; D012254:Ribavirin; D000068817:Epoetin Alfa; C417083:peginterferon alfa-2b