Peginterferon plus ribavirin is standard therapy for adults with chronic hepatitis C. As no data are available for children, the aim of the study was to evaluate the efficacy and tolerability of peginterferon alfa-2b in combination with ribavirin in chronically infected children. Genotypes, alanine aminotransferase levels, and different routes of viral transmission were considered. In an open-labeled, uncontrolled pilot study, 62 children and adolescents (range, 2-17 years) were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 g/kg body weight once per week plus oral ribavirin (15 mg/kg ؋ day) for 48 weeks. Sixty-one patients completed the study. Twenty-three children discontinued therapy after 6 months according to study protocol. P eginterferon alfa and ribavirin is established as standard treatment in adults with chronic hepatitis C (HCV). International studies have yielded sustained viral response rates (SVR) between 44% and 75% according to the genotype. 1,2 Whereas interferon alfa-2b and ribavirin has been approved for individuals between 3 and 18 years of age in the United States, the indication for therapy in children and adolescents is still debated in many countries. One reason may be that ribavirin has teratogenic or embryocidal effects in animals. The risk of ribavirin as a carcinogen in humans has not been established. For more than 20 years, the substance has been used in infants for other indications, such as respiratory syncytial virus infection.The usage of peginterferon has improved response rates in adults by approximately 10% compared with a treatment regimen with interferon-alfa and ribavirin. Moreover, dosing of peginterferon once per week is another considerable advantage. No treatment study with peginterferon-alfa and ribavirin in children and adolescents with chronic HCV has been published so far.Chronic HCV in childhood features particular issues regarding mode of infection, immunological competence, and inflammatory activity. Vertical infection is the most important route of viral transmission. 3 These children are infected at a phase of high immune tolerance. A considerable number of young individuals display normal aminotransferases, reflecting a low inflammatory activity. Despite a relatively low disease progression during the first 15 to 20 years of life, severe liver disease occasionally occurs during childhood. In vertically infected patients, long-term spontaneous clearance of chronic HCV is low, SVR, sustained viral response; HCV RNA, hepatitis C virus ribonucleic acid; ALT, alanine aminotransferase. From the

The activation of mammalian origins of replication depends so far on ill understood epigenetic events, such as binding of transcription factors, chromatin structure, and nuclear localization. Understanding these mechanisms is not only a scientific challenge but also represents a prerequisite for the rational design of nonviral episomal vectors for mammalian cells. In this paper, we demonstrate that a tetramer of a 155-bp minimal nuclear scaffold͞matrix attached region DNA module linked to an upstream transcription unit is sufficient for replication and mitotic stability of a mammalian episome in the absence of selection. Fluorescence in situ hybridization analyses, crosslinking with cis-diammineplatinum(II)-dichloride and chromatin immunoprecipitation demonstrate that this vector associates with the nuclear matrix or scaffold in vivo by means of specific interaction of the nuclear scaffold͞matrix attached region with the nuclear matrix protein SAF-A. Results presented in this paper define the minimal requirements of an episomal vector for mammalian cells on the molecular level.DNA replication ͉ mitotic stability ͉ nuclear matrix ͉ SAF-A