A randomized trial of prolonged high dose of interferon plus ribavirin for hepatitis C patients nonresponders to interferon alone.
Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.
Fattovich
G
G
Servizio Autonomo Clinicizzato di Gastroenterologia, Università di Verona, Verona, Italy. giovanna_fattovich@tin.it
Zagni
I
I
Ribero
M L
ML
Castagnetti
E
E
Minola
E
E
Lomonaco
L
L
Scattolini
C
C
Fabris
P
P
Boccia
S
S
Giusti
M
M
Abbati
G
G
Felder
M
M
Rovere
P
P
Redaelli
A
A
Tonon
A
A
Tomba
A
A
Montanari
R
R
Paternoster
C
C
Distasi
M
M
Fornaciari
G
G
Tositti
G
G
Rizzo
C
C
Suppressa
S
S
Pantalena
M
M
Noventa
F
F
Tagger
A
A
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin