HCV-RNA SERUM LEVELS IN CHILDREN WITH CHRONIC HEPATITIS C AND RESPONSE TO INTERFERON THERAPY

Abstract

Recently it has been reported that low baseline serum HCV-RNA levels and early loss of serum HCV-RNA on IFN therapy can predict a long-term response to IFN therapy in adults with chronic hepatitis C (CHC). Little information is available about viraemic changes during IFN therapy in children with CHC. Aim: to evaluate serum HCV-RNA levels before and during IFN therapy in children with CHC and compare virological and biochemical response rates. Methods: 25 consecutive children (13 males; mean age 7.9 yrs; range 3.6-11.5 yrs) affected by CHC were enroled to receive treatment with recombinant-alfa2b IFN (5MU/m2 t.i.w.) for 12 months. IFN therapy was suspended before time in case of severe side effects including hypertransaminasemia (>6 times the upper reference limit) or if no reduction of ALT after 6 months of therapy occurred. Patients' sera were tested for liver function tests and HCV-RNA serum levels by branched DNA signal amplification (b-DNA) assay (Chiron HCV-RNA 2.0; level of sensitivity 0.2 × 106 Eq/ml) at the following times: 2 and 1 week before IFN therapy, weekly for the first 3 weeks of treatment, and therafter monthly until the suspension of IFN. Results: At the present, 15 patients have completed the entire course of therapy, in remaning 10 patients IFN was suspended before time according to protocol. Before therapy, median HCV-RNA serum levels were 0.90 ×106 Eq/ml (range: 0.10-20.18), median ALT serum levels were 74 IU/L (range: 41-219; normal values <35 IU/L). At the end of treatment 8/25 were considered biochemical responders (BR) because ALT serum levels became normal during the treatment and persisted normal until the suspension, the remaining were biochemical nonresponders (NBR). In 11 patients (5 BR), viremia fell below the level of sensitivity already after the second dose of IFN. During the course of therapy, only 2 patients (both BR) showed undetectable levels of HCV-RNA levels for the whole period of treatment; 7 patients (all NBR) showed HCV-RNA levels persistently elevated; in the remaining patients viremia was fluctuating with phases of reduction below the level of sensitivity of the test. At the end of therapy, 12 patients (7 BR) had undetectable levels of serum HCV-RNA. Although no significant difference between pretreatment values of HCV-RNA serum levels between BR (median 0.29 ×106 Eq/ml; range: 0.10-1.62) and BNR (median 1.04 ×106 Eq/ml; range: 0.15-20.18) was found, none of BR had basal values of HCV-RNA >1.62 × 106 Eq/ml. Conclusions: an early reduction of serum HCV-RNA levels occurred in 44% of CHC patients treated with IFN, but only in 8% persisted for the entire course of therapy; persistent biochemical and virological responses may be predicted by low pretreatment HCV-RNA levels; the present study did not confirm the virological response rates observed in previous studies in whom a single evaluation of HCV-RNA levels was performed at the end of therapy.