Reinforced regimen of interferon alfa-2a reduces the incidence of cirrhosis in patients with chronic hepatitis C: a multicentre randomised trial. Multicentre GER-CYT-04 Group.
OBJECTIVE
Our aim was to assess and compare the long-term effect of interferon at standard (6 months) and reinforced dose and duration regimens in chronic hepatitis C.


METHODS
A multicentre institutional trial included 244 previously untreated patients with chronic hepatitis C, without cirrhosis, who were randomly allocated to either standard (3 MU thrice a week for 24 weeks; n=120) or reinforced (6 MU daily for 12 days, 6 MU thrice a week for 22 weeks, 3 MU thrice a week for 24 weeks; n=124) regimens. The main endpoint was sustained ALT response at 72 weeks (18 months); secondary end-points were virological (branched DNA and PCR) and histological responses (incidence of cirrhosis) at month 18.


RESULTS
Sustained ALT response was observed in five patients (4%, 95% confidence interval 0-8%) in the standard group and in 21 patients (18%, 95% confidence interval 11-25%), from the reinforced group (p=0.002), in agreement with virological response in 21 (81%) patients. Cirrhosis at month 18 was observed in ten (10%) patients in the standard group and one (1%) in the reinforced group (p=0.004).


CONCLUSIONS
The standard regimen of interferon, in chronic hepatitis C, confers a minimal sustained response rate at 18 months and may not prevent the occurrence of cirrhosis. Reinforced regimens allow sustained response to be reached in a limited number of patients and reduce the risk of cirrhosis during 18 months of follow-up.
Degos
F
F
Service d'Hépatogastroentérologie, Hôpital Beaujon, Clichy, France.
Daurat
V
V
Chevret
S
S
Gayno
S
S
Bastie
A
A
Riachi
G
G
Bartolomei-Portal
I
I
Barange
K
K
Moussalli
J
J
Naveau
S
S
Bailly
F
F
Chaumet-Riffaud
P
P
Chastang
C
C
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D002985:Clinical Protocols; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000150:complications / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011336:Probability; D011994:Recombinant Proteins; D013997:Time Factors
D000998:Antiviral Agents; D004279:DNA, Viral; D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000410:Alanine Transaminase