Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data.
OBJECTIVE
Retreatment with a combination of alpha interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies.


METHODS
To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000-1200 mg/daily depending on body weight) was given for 24-60 (mean 39.5) weeks.


RESULTS
Biochemical end of treatment and sustained responses were observed in 271/581 (46.6%; 95% confidence interval (CI) 42.6-50.7%) and in 109/581 (18.7%; 95% CI 15.6-22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% CI 34.6-42.9%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7%; 95% CI 12.8-18.8%). Fifty four of 581 patients (9.2%; 95% CI 7.0-11.7%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment gamma-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008).


CONCLUSIONS
The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal gamma-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%.
Cammà
C
C
Istituto Metodologie Diagnostiche Avanzate, Consiglio Nazionale delle Ricerche, and Cattedra e Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy. camma@ismeda.pa.cnr.it
Bruno
S
S
Schepis
F
F
Lo Iacono
O
O
Andreone
P
P
Gramenzi
A G
AG
Mangia
A
A
Andriulli
A
A
Puoti
M
M
Spadaro
A
A
Freni
M
M
Di Marco
V
V
Cino
L
L
Saracco
G
G
Chiesa
A
A
Crosignani
A
A
Caporaso
N
N
Morisco
F
F
Rumi
M G
MG
Craxì
A
A
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000627:therapeutic use*; D017211:Treatment Failure; D005723:gamma-Glutamyltransferase / Q000097:blood
D000998:Antiviral Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D012254:Ribavirin; D005723:gamma-Glutamyltransferase