Iron depletion before HCV antiviral therapy: a pilot, randomized, controlled trial.
It is not known whether iron depletion before pegylated IFN or combination treatment improves sustained virological response (SVR) rate in patients with chronic hepatitis C, despite its use in clinical practice in this setting. We aimed to investigate whether blood letting improves the efficacy (SVR) and tolerability of PEG-IFNalpha2b + Ribavirin in chronic hepatitis C patients. Patients with chronic hepatitis C and ferritin >100 ng/mL were randomized to: (1) repeated phlebotomies to obtain a ferritin level <50 ng/mL followed by pegylated-Interferon alpha2b + ribavirin (active arm); or (2) pegylated-Interferon alpha2b + ribavirin (control arm). Primary endpoint was SVR rate, secondary endpoint was frequency of clinical and laboratory grade 3-4 adverse events. Thirty-three patients were enrolled in the study (19 in active arm, 14 in control arm). The 19 patients in the active arm underwent a median of 5 phlebotomies (range: 1-9) to achieve the targeted ferritin (<50 ng/mL). Phlebotomies significantly reduced ferritin, iron, transferrin saturation, aspartate aminotransferase, alanine aminotransferase, and hemoglobin levels. Platelet count significantly increased, whereas HCV-RNA levels remained unchanged. After antiviral therapy overall SVR was 31.6% in active arm and 21.4% in control arm (P = 0.698). Considering only the 18 patients who were naive to antiviral therapy, SVR was 60% in active arm versus 25% in control arm (P = 0.188). Tolerability, drug dose reduction or withdrawal were similar in the two arms. In conclusion phlebotomies do not increase the overall efficacy of antiviral therapy. However, the strong trend to higher SVR in naive patients undergoing phlebotomies warrants further investigation.
Gentile
Ivan
I
Department of Public Medicine and Social Security, Section of Infectious Diseases, University Federico II, Naples, Italy. ivan.gentile@alice.it
Viola
Chiara
C
Paesano
Luigi
L
D'Onofrio
Marcello
M
D'Agostino
Elio
E
Cerini
Raimondo
R
Borrelli
Francesco
F
Piazza
Marcello
M
Borgia
Guglielmo
G
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005293:Ferritins / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D014168:Transferrin / Q000032:analysis
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014168:Transferrin; D011092:Polyethylene Glycols; D012254:Ribavirin; D005293:Ferritins; D007501:Iron; C417083:peginterferon alfa-2b