Interferon-alpha plus ribavirin in chronic hepatitis C resistant to previous interferon-alpha course: results of a randomized multicenter trial.
OBJECTIVE
Interferon-alpha plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter randomized trial, we evaluated the efficacy of this association for interferon-alpha resistant chronic hepatitis C.


METHODS
Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-alpha were randomized to receive either ribavirin (800 mg/day) plus leucocytic interferon-alpha (3 mega units thrice weekly) or the same dose of interferon-alpha alone, for 6 months. Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies.


RESULTS
At the end of treatment, aminotransferase levels become normal in 9/26 patients receiving combination therapy (35% [confidence interval, 16% to 53%]) and in 2/24 receiving interferon-alpha alone (8% [confidence interval, -3% to 19%]) (p = 0.03). Aminotransferase normalization was never associated with hepatitis C virus RNA clearance. All patients with normal aminotransferase relapsed after discontinuation of therapy. At the end of treatment, mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy, but returned to pretreatment values 6 months thereafter. No histological improvement was observed in either group.


CONCLUSIONS
There is no indication for treatment with interferon-alpha at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-alpha.
Andreone
P
P
Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, Università di Bologna, Italy.
Gramenzi
A
A
Cursaro
C
C
Sbolli
G
G
Fiorino
S
S
Di Giammarino
L
L
Miniero
R
R
D'Errico
A
A
Gasbarrini
G
G
Bernardi
M
M
D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007249:Inflammation; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin