Pegylated interferon for chronic hepatitis C in children affects growth and body composition: Results from the pediatric study of hepatitis C (PEDS-C) trial

Article (PDF Available)inHepatology 56(2):523-31 · August 2012with69 Reads
DOI: 10.1002/hep.25690 · Source: PubMed
Weight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated interferon alpha-2a (Peg-IFN-α2a) ± ribavirin in the Pediatric Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual-energy X-ray absorptiometry scan, as well as dietary and activity assessments during and after treatment. One hundred and fourteen (55% male) children, with a mean age of 11 ± 3 years, were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into three groups according to duration of treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to 0.50 z score were observed for weight, height, and BMI while on therapy among all groups (P ≤ 0.01, compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ) score. Though weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long-treatment duration group (P = 0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores, and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment. CONCLUSIONS: Peg-IFN-α2a was associated with significant changes in body weight, linear growth, BMI, and body composition in children. These effects were generally reversible with cessation of therapy, although HAZ scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.

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Available from: Kathleen B Schwarz, Sep 07, 2014
    • "This is particularly true for health-care workers following children with systemic illnesses, where weight loss may reflect disease activity even before it impacts on statural growth [22,23]. In both infants and older children, correct interpretation of BMI changes also requires concurrent inspection of height and weight-for-age242526. InFigure 3 Bootstrap estimates of centile precision: smoothed centiles for girls (A) BMI, weight, and height were first fitted to the original NCHS-R data (N = 11,193). "
    [Show abstract] [Hide abstract] ABSTRACT: For ages 5-19 years, the World Health Organization (WHO) publishes reference charts based on 'core data' from the US National Center for Health Statistics (NCHS), collected from 1963-75 on 22,917 US children. To promote the use of body mass index in older children, weight-for-age was omitted after age 10. Health providers have subsequently expressed concerns about this omission and the selection of centiles. We therefore sought to extend weight-for-age reference curves from 10 to 19 years by applying WHO exclusion criteria and curve fitting methods to the core NCHS data and to revise the choice of displayed centiles. WHO analysts first excluded ~ 3% of their reference population in order to achieve a "non-obese sample with equal height". Based on these exclusion criteria, 314 girls and 304 boys were first omitted for 'unhealthy' weights-for-height. By applying WHO global deviance and information criteria, optimal Box-Cox power exponential models were used to fit smoothed weight-for-age centiles. Bootstrap resampling was used to assess the precision of centile estimates. For all charts, additional centiles were included in the healthy range (3 to 97%), and the more extreme WHO centiles 0.1 and 99.9% were dropped. In addition to weight-for-age beyond 10 years, our charts provide more granularity in the centiles in the healthy range -2 to +2 SD (3-97%). For both weight and BMI, the bootstrap confidence intervals for the 99.9th centile were at least an order of magnitude wider than the corresponding 50th centile values. These charts complement existing WHO charts by allowing weight-for-age to be plotted concurrently with height in older children. All modifications followed strict WHO methodology and utilized the same core data from the US NCHS. The additional centiles permit a more precise assessment of normal growth and earlier detection of aberrant growth as it crosses centiles. Elimination of extreme centiles reduces the risk of misclassification. A complete set of charts is available at the CPEG web site (
    Full-text · Article · Feb 2014
    • "Schwarz et al, 2011 [8] Jonas et al, 2012 [39] Decrements of up to 0.5 z score were observed for weight, height, and body mass index in many patients during the treatment phase. Longer treatment durations were associated with greater decreases. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin (RBV) in children and adolescents with chronic hepatitis C virus (HCV). Methods: Medline, Embase, and Cochrane Central Register of Controlled Trials were searched. Clinical trials examining peg-IFN alfa-2a or peg-IFN alfa-2b plus RBV among persons ages 3-18 years with HCV were included. Data were abstracted for complete early virologic response (EVR), sustained virologic response (SVR), relapse, treatment discontinuations, hematologic and dermatologic adverse events, and growth inhibition. Results: Eight trials met the inclusion criteria. Results indicate that 70% of subjects (95% confidence interval [CI], 58%-81%) achieved EVR, and 58% (95% CI, 53%-64%) achieved SVR. EVR and SVR were higher for those with HCV genotypes 2/3 than 1/4. Discontinuation due to adverse events and discontinuation due to viral breakthrough were each 4%, discontinuation due to a lack of response was 15%, and relapse was 7%. Anemia, neutropenia, leukopenia, and thrombcytopenia were 11%, 32%, 52%, and 5%, respectively. Alopecia, injection site erythema, and pruritus were 13%, 27%, and 10%, respectively. Small growth inhibitions were observed during treatment. Conclusion: The results of this meta-analysis indicate that peg-IFN/RBV combination treatment is effective and safe in treating children and adolescents with HCV.
    Full-text · Article · Dec 2012
  • [Show abstract] [Hide abstract] ABSTRACT: HBV and HCV are the predominant causes of chronic viral hepatitis in children and adults. The main purposes of the present review are to provide the reader with a comprehensive overview of the currently available therapies for chronic hepatitis B and C in children and to critically review the current guidelines and indications for treatment provided by the major international societies and by the consensus of expert panels. Overall, a conservative approach is generally warranted in children with chronic hepatitis B. For HCV, the high effectiveness of pegylated interferon and ribavirin in children with genotype 2 or 3 chronic infection supports the decision to treat. For genotype 1 infection the encouraging results of the use of direct antiviral agents in adults suggest a more conservative approach.
    Article · Oct 2012
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