Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: a meta-analysis.
OBJECTIVE
Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis.


METHODS
MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourteen trials were included in the meta-analysis. Data on study populations, interventions, and outcomes were extracted from trials using a random-effects model. Primary outcome was the SVR rate.


RESULTS
The pooled estimate of SVR rate was 16.3% (95% Confidence Interval - 95% CI, 8.3-29.6%). There was a significant heterogeneity among studies (p<0.0001). Heterogeneity was less apparent in studies that included fewer patients with cirrhosis or overweight. By meta-regression, higher SVR rate was observed in trials with a lower prevalence of subjects with genotype 1 infection and with fewer overweight patients. The use of a 24-week retreatment stopping rule did not affect SVR rate.


CONCLUSIONS
The overall modest efficacy argues against an indiscriminate retreatment with PEG-IFN and ribavirin of all non-responders. Restricting retreatment to non-overweight patients or to those with genotype 2 or 3 infection, using a 24-week retreatment stopping rule, would optimize the potential benefit with a scarce likelihood of missing a curative response.
Cammà
Calogero
C
Cattedra di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy. carlo.camma@unipa.it
Cabibbo
Giuseppe
G
Bronte
Fabrizio
F
Enea
Marco
M
Licata
Anna
A
Attanasio
Massimo
M
Andriulli
Angelo
A
Craxì
Antonio
A
D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*
D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin