Interferon-α and Ribavirin in Treating Children and Young Adults  With Chronic Hepatitis C After Malignancy

Lackner, Herwig; Moser, Andrea; Deutsch, J.; Kessler, Harald H.; Benesch, Martin; Kerbl, Reinhold; Schwinger, Wolfgang; Dornbusch, Hans-Jürgen; Preisegger, Karl‐Heinz; Urban, Christian

doi:10.1542/peds.106.4.e53

Cited by 69 publications

(66 citation statements)

References 26 publications

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“…Our studies demonstrate that interferon alfa-2b in combination with oral ribavirin is effective and reasonably safe for the treatment of childhood chronic hepatitis C. Infection with HCV genotypes 2 or 3, and lower level of serum HCV RNA at baseline in HCV genotype 1, are associated with higher virological response rates. These results are consistent with those reported in small pediatric pilot [18][19][20][21] and large adult studies. 7,8 SVR rates in children with chronic HCV given interferon alfa-2b with ribavirin in these studies are higher than in those using interferon alone (46% vs. 36%, respectively).…”

Section: Discussionsupporting

confidence: 93%

“…In agreement with published pediatric data, [18][19][20][21] decreases in mean linear growth and weight associated with treatment were observed in these studies. However, after discontinuation of treatment, compensatory increases were noted in both height and weight, reaching nearbaseline pretreatment values by the end of follow-up.…”

Section: Discussionsupporting

confidence: 91%

“…Most events, such as insomnia, irritability, and somnolence, were mild to moderate in severity. In addition, depression, a side effect not previously reported in children with chronic HCV infection given interferon alone 23 or with ribavirin, [18][19][20][21] occurred in 13% of subjects. This may reflect the fact that the protocols were designed to identify and monitor depressive symptoms.…”

Section: Discussionmentioning

confidence: 97%

“…The overall pattern of adverse events, hematological changes, and discontinuations from treatment is consistent with that seen in pediatric subjects treated with interferon alone or in combination with ribavirin. [18][19][20][21] The adverse event profile in children is also similar to that seen in adults treated with comparable regimens. 7,8 The most common adverse events consisted of influenza-like symptoms and gastrointestinal complaints, including fever, headache, anorexia, vomiting, abdominal pain, myalgia, and nausea.…”

Section: Discussionmentioning

confidence: 98%

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Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics

et al. 2005

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Chronic hepatitis C virus (HCV) infection is usually asymptomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84%) than in those with HCV genotype 1 (36%). Adverse events led to dose modification in 37 (31%) and discontinuation in 8 (7%). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar between children and adults. In conclusion, interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus. (HEPATOLOGY 2005;42:1010-1018.) H epatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. Although our understanding about the natural history and pathobiology of HCV infection in children is incomplete, it has been associated with significant liver disease, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma in this population. 1-4 Approximately 10% to 20% of adults 5 and 36% of children 6 treated with interferon alone achieve long-term virological remission. The addition of ribavirin to interferon-based regimens markedly improves virological responses in adults. 7,8 Limited data are available regarding the use of interferon alfa with ribavirin in children. Therefore, the aim of our studies was to evaluate the efficacy, safety, and pharmacokinetics of interferon alfa-2b in combination with ribavirin for the treatment of chronic HCV infection in children. Patients and Methods Study DesignA clinical program consisting of two studies was initiated to evaluate the efficacy, safety, and pharmacokinetics of interferon alfa-2b (Intron A, Schering-Plough, KenAbbreviations: HCV, hepatitis C virus; MIU, million international units; PCR, polymerase chain reaction; TSH, thyroid-stimulating hormone; ALT, alanine aminotransferase; SVR, sustained virological response. From the

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

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Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics

et al. 2005

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“…Some studies using interferon-alfa and ribavirin yielded overall response rates between 41.7% and 61%. [7][8][9][10][11][12] Most treated children in these studies had been infected by parenteral transmission. Because treatment with peginterferon-alfa and ribavirin yielded a further increase by approximately 10% compared with combination therapy with non-pegylated interferon-alfa in adults, it was obvious to offer the treatment to children and adolescents as well.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

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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

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Chronic Hepatitis

Davison¹

2003

Diseases of the Liver and Biliary System in Children

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Interferon-α and Ribavirin in Treating Children and Young Adults With Chronic Hepatitis C After Malignancy

Abstract: As demonstrated in adults with chronic hepatitis C, treatment with IFN-alpha and RBV also seems to be an effective and safe therapeutic option for children and adolescents with chronic hepatitis C after malignancy.

Cited by 69 publications

References 26 publications

Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics

Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics

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

Chronic Hepatitis

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