The combination of interferon (IFN) and ribavirin (RIBA) has efficacy in previously non-responder (NR) or relapser (REL) HCV patients. However, the effect of increased dose of IFN associated with RIBA is not known. The aim of this study was to evaluate different IFN dose in combination with RIBA in NR or REL patients.We randomised 102 patients with biopsy-proven chronic HCV hepatitis to receive either 3 or 5 MU of recombinant IFN three times a week and RIBA (1000-1200 mg/die) for 6 months and followed for additional 6 months. Patients with cirrhosis were excluded from the study. The treatment was stopped at 4 months for cases with abnormal ALT levels and HCV-RNA positivity. The patients with undetectable HCV-RNA and normal ALT at the end of the treatment were defined as complete responders (CR), and those with the same state the end of follow-up were defined as long-term responders (LTR). There were 52 non-responders and 58 relapsers to prior IFN treatment. Mean age and histological severity of liver disease was comparable in the four groups. Four patients (4%) dropped out because skin lesions or severe anaemia. A large fraction of patients (68 cases, 64 %) developed mild anaemia but therapy was not discontinued. Full follow-up data are available on 102 cases. IFN 3 MU 3 times a week End of treatment End follow-up 25 previous NR 4 CR (16%) 21 NR (84%) 4 LTR (16%) 25 previous REL 15 CR (60%) 10 NR (40%) 12 LTR (46%) IFN 5 MU 3 times a week 27 previous NR 18 CR (66%) 9 NR (33%) 12 LTR (44%) 25 previous REL 22 CR (88%) 3 NR (12%) 17 LTR (68%) There was a statistically significant difference between previous REL and NR either at the end of the treatment and of the follow-up. There was difference between previous REL subjects randomised to receive 3 or 5 MU at the end of the therapy but not at the end of the follow-up. On the contrary, in previous NR an increased dose of IFN obtained a statistically (p<0.03) improvement of responses. Interestingly, a fraction (10-40%) of previous REL became NR at the combination therapy, this could indicate the appearance of viral quasispecies or genotypes highly resistant to antiviral drugs. In conclusions, when used in combination with RIBA, 5MU of IFN is able to enhance the response rate compared with 3MU, especially in previous NR. In NR or REL cases after combination therapy, new therapeutical approaches are needed.

Randomized trial of combination therapy in relapser or non-responder HCV patients

POZZATO, GABRIELE
2000-01-01

Abstract

The combination of interferon (IFN) and ribavirin (RIBA) has efficacy in previously non-responder (NR) or relapser (REL) HCV patients. However, the effect of increased dose of IFN associated with RIBA is not known. The aim of this study was to evaluate different IFN dose in combination with RIBA in NR or REL patients.We randomised 102 patients with biopsy-proven chronic HCV hepatitis to receive either 3 or 5 MU of recombinant IFN three times a week and RIBA (1000-1200 mg/die) for 6 months and followed for additional 6 months. Patients with cirrhosis were excluded from the study. The treatment was stopped at 4 months for cases with abnormal ALT levels and HCV-RNA positivity. The patients with undetectable HCV-RNA and normal ALT at the end of the treatment were defined as complete responders (CR), and those with the same state the end of follow-up were defined as long-term responders (LTR). There were 52 non-responders and 58 relapsers to prior IFN treatment. Mean age and histological severity of liver disease was comparable in the four groups. Four patients (4%) dropped out because skin lesions or severe anaemia. A large fraction of patients (68 cases, 64 %) developed mild anaemia but therapy was not discontinued. Full follow-up data are available on 102 cases. IFN 3 MU 3 times a week End of treatment End follow-up 25 previous NR 4 CR (16%) 21 NR (84%) 4 LTR (16%) 25 previous REL 15 CR (60%) 10 NR (40%) 12 LTR (46%) IFN 5 MU 3 times a week 27 previous NR 18 CR (66%) 9 NR (33%) 12 LTR (44%) 25 previous REL 22 CR (88%) 3 NR (12%) 17 LTR (68%) There was a statistically significant difference between previous REL and NR either at the end of the treatment and of the follow-up. There was difference between previous REL subjects randomised to receive 3 or 5 MU at the end of the therapy but not at the end of the follow-up. On the contrary, in previous NR an increased dose of IFN obtained a statistically (p<0.03) improvement of responses. Interestingly, a fraction (10-40%) of previous REL became NR at the combination therapy, this could indicate the appearance of viral quasispecies or genotypes highly resistant to antiviral drugs. In conclusions, when used in combination with RIBA, 5MU of IFN is able to enhance the response rate compared with 3MU, especially in previous NR. In NR or REL cases after combination therapy, new therapeutical approaches are needed.
2000
HCV; interferon therapy
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2559475
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