Background: Therapy of chronic hepatitis C non-responders to interferon mon
otherapy with standard doses of interferon plus ribavirin is usually ineffe
Aim: To evaluate the efficacy and tolerability of high-dose prolonged combi
nation retreatment in non-responder patients.
Methods: Patients were retreated for 6 months with 6 MU alpha IFN on altern
ate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients conti
nued therapy for an additional 6 months.
Results: Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11
with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA
negative but six of them discontinued therapy because of adverse events. A
sustained response was achieved in 28% of patients (11/40). A sustained re
sponse was more frequent among patients with genotype non-1b then in those
with genotype 1b (67 vs. 21%, P = 0.005) and clearance of HCV-RNA in the fi
rst 3 months had a high predictive value for sustained response (100% of su
stained responders vs. 24% of non-responders, P = 0.0001).
Conclusions: High-dose prolonged combination therapy in non-responders to I
FN monotherapy leads to a higher rate of sustained response than the standa
rd combination regimen. Tolerability may be a rate-limiting factor. Maximal
effectiveness can be predicted in patients with non-1b genotype and in tho
se who clear HCV-RNA soon after starting retreatment.