Peginterferon alfa-2b plus ribavirin treatment in children and adolescents with chronic hepatitis C

Abstract

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

Management of Chronic Hepatitis C: Consensus Guidelines

“…Standard IFN 3 MU/m 2 three times a week with ribavirin 15 mg/kg/day for 48 weeks yielded an SVR of 40% to 60% overall, and 70% to 100% in genotype 2 or 3 infection (79). PEG IFN-alpha-2a or -2b and ribavirin have been used in small numbers of HCV-infected children with SVR rates of 43% to 59% (higher in genotypes 2 and 3 than in genotypes 1 and 4) (80,81). Whether EVR can be used, as in adults, to stop therapy early in patients destined to be nonresponders is not clear.…”

Hepatitis C genotype 4: The past, present, and future

“…In addition, children have fewer comorbidities than adults and parental motivation enhances adherence to treatment. Children also tolerate currently available therapies better than adults, with mild adverse effects [156] . Economically, the cost of treatment is less than that in adults (fewer drugs used).…”

Hepatitis C virus infection in children and adolescents

“…Currently, the only Food and Drug Administration‐approved options for children with chronic HCV infection are ribavirin (RBV) and pegylated‐interferon (PEG‐IFN). While sustained viral responses (SVRs) have improved over the last several decades from ∼16% with IFN monotherapy to >50% with the combination of RBV and PEG‐IFN, multiple studies have shown that SVR rates remain frustratingly low compared to adults with access to DAA regimens 6, 13, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116. Consequently, in the absence of approved DAA therapies in the United States, the chance of attaining SVR in HCV‐infected children and adolescents is little more than 50% (Table 4).…”