Fixed versus titrated interferon-alpha 2B in chronic hepatitis C. A randomized controlled multicenter trial. The Swiss Association for the Study of the Liver.
OBJECTIVE
Interferon has become the mainstay of treatment of chronic hepatitis C; however, duration of treatment and dose remain unresolved questions. The present study aimed to compare standard dose interferon with a titrated dose regimen carried out for 1 year.


METHODS
This was a randomized, controlled multicenter trial. Patients with chronic hepatitis C were randomly allocated to a control group (n = 30), to a fixed dose group (n = 31) where interferon-alpha 2b 3 MU thrice weekly was given for 1 year or a titrated group (n = 34) where interferon was titrated starting at 5 MU thrice weekly to the lowest dose keeping the patient in remission as assessed by a normal ALT value. Liver biopsies were obtained before and at the end of treatment; in addition, galactose elimination capacity was measured as a measure of cytosolic function.


RESULTS
In the control, fixed and titrated groups a complete response was achieved in 2/29, 10/28 and 15/31, respectively (p < 0.001 in favor of treatment, p = n.s. for the two treatments). The corresponding figure for sustained response was 1/29, 5/28 and 6/ 31 (p = n.s). In the titrated group, a complete (sustained) response was achieved with 5 MU in 2 (2), with 4 MU in 1 (0), with 3 MU in 4 (0), with 2 MU in 3 (0) and with 1 MU in 5 (4). Liver biopsy score and galactose elimination capacity improved significantly in responders but not in treatment failures.


CONCLUSIONS
Both fixed and titrated dosing of interferon given for 1 year induced virus clearance in only a minority of treated patients. However, in a small number of patients, a complete and sustained response can be achieved with low doses of interferon. Dose titration could be an interesting approach to decreasing the cost and side effects in the treatment of chronic hepatitis C.
Department of Clinical Pharmacology, University of Berne, Switzerland.
J
J
Reichen
L
L
Bianchi
H
H
Bühler
N
N
Dolivo
J J
JJ
Gonvers
D
D
Lavanchy
P J
PJ
Malé
E L
EL
Renner
M
M
Solioz
M
M
Schmid
A
A
Zimmermann
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D005690:Galactose / Q000378:metabolism; D006526:Hepatitis C / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013997:Time Factors; D017186:Titrimetry; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000410:Alanine Transaminase; D005690:Galactose