BACKGROUND: Although no therapeutic regimen has received Food and Drug Administration approval for treating children with chronic hepatitis C viral infection (CHC), there have been a number of pediatric interferon-alpha (IFN-alpha) trials. The purpose of this study was to perform a critical review of these trials to determine 1) end-of-treatment (ETR) and sustained-response (SR) rates, 2) predictors of response to therapy, and 3) safety of and tolerance to IFN-alpha in children with CHC. METHODS: Relevant studies in the English-language medical literature and abstracts (January 1990 through November 2000) were identified by searching for manuscripts that contained the key words "children," "hepatitis C," and "interferon." Trials were considered eligible for inclusion in this analysis if criteria for treatment included positive serum polymerase chain reaction for hepatitis C virus RNA (HCV PCR). RESULTS: Twenty published manuscripts of the use of IFN-alpha in children with CHC were found, of which 12 met our inclusion criteria. Twenty-two abstracts, of which seven met our inclusion criteria, were identified. In the 19 included trials, 366 treated and 105 untreated children were observed; five countries were represented. Average ETR was 54% (0%-91%) and average SR was 36% (0%-73%). The SR in children with genotype 1 was 27% versus 70% for nongenotype 1 ( P = 0.001). Five of 105 (5%) untreated controls exhibited spontaneous viral clearance. CONCLUSIONS: To date, there is no published large-scale, multicenter, prospective, placebo-controlled randomized trial of the use of IFN-alpha in children with CHC. The data in this review suggest that IFN-alpha in children with CHC does have reasonable efficacy and safety. This review highlights the need for a more systematic design of future pediatric CHC trials. Ideally, such trials would be large scale, prospective, and controlled, and would include HCV genotype and viral load, histology, quality of life measures, and systematic recording of adverse events and of effects of therapy on growth and development.
BACKGROUND: Although no therapeutic regimen has received Food and Drug Administration approval for treating children with chronic hepatitis C viral infection (CHC), there have been a number of pediatric interferon-alpha (IFN-alpha) trials. The purpose of this study was to perform a critical review of these trials to determine 1) end-of-treatment (ETR) and sustained-response (SR) rates, 2) predictors of response to therapy, and 3) safety of and tolerance to IFN-alpha in children with CHC. METHODS: Relevant studies in the English-language medical literature and abstracts (January 1990 through November 2000) were identified by searching for manuscripts that contained the key words "children," "hepatitis C," and "interferon." Trials were considered eligible for inclusion in this analysis if criteria for treatment included positive serum polymerase chain reaction for hepatitis C virus RNA (HCV PCR). RESULTS: Twenty published manuscripts of the use of IFN-alpha in children with CHC were found, of which 12 met our inclusion criteria. Twenty-two abstracts, of which seven met our inclusion criteria, were identified. In the 19 included trials, 366 treated and 105 untreated children were observed; five countries were represented. Average ETR was 54% (0%-91%) and average SR was 36% (0%-73%). The SR in children with genotype 1 was 27% versus 70% for nongenotype 1 ( P = 0.001). Five of 105 (5%) untreated controls exhibited spontaneous viral clearance. CONCLUSIONS: To date, there is no published large-scale, multicenter, prospective, placebo-controlled randomized trial of the use of IFN-alpha in children with CHC. The data in this review suggest that IFN-alpha in children with CHC does have reasonable efficacy and safety. This review highlights the need for a more systematic design of future pediatric CHC trials. Ideally, such trials would be large scale, prospective, and controlled, and would include HCV genotype and viral load, histology, quality of life measures, and systematic recording of adverse events and of effects of therapy on growth and development.
Authors: Kathleen B Schwarz; Regino P Gonzalez-Peralta; Karen F Murray; Jean P Molleston; Barbara A Haber; Maureen M Jonas; Philip Rosenthal; Parvathi Mohan; William F Balistreri; Michael R Narkewicz; Lesley Smith; Steven J Lobritto; Stephen Rossi; Alexandra Valsamakis; Zachary Goodman; Patricia R Robuck; Bruce A Barton Journal: Gastroenterology Date: 2010-10-28 Impact factor: 22.682