Efficacy and Safety of Peginterferon-Alpha 2b and Ribavirin Combination Therapy in Children With Chronic Hepatitis C Infection

Article · February 2008with16 Reads
DOI: 10.1097/INF.0b013e318159836c · Source: PubMed
Abstract
Interferon (IFN)-alpha2b plus ribavirin is approved for treatment of hepatitis C in children; however, little is known about efficacy and tolerability of pegylated IFN (PEG-IFN)-alpha2b in this population. The objective of this study was to test the efficacy and safety of PEG-IFN-alpha2b plus ribavirin in children with chronic hepatitis C. Thirty children 3-16 years of age who had detectable hepatitis C virus (HCV) RNA for >or=3 years after exposure and elevated alanine aminotransferase values received PEG-IFN-alpha2b 1.0 microg/kg/wk plus ribavirin 15 mg/kg/d for 24 weeks (genotype 2/3) or 48 weeks (genotype 1/4). The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50 IU/mL) at week 24 of follow-up. SVR was achieved in 50% of patients (3/3 genotype 3; 12/27 genotype 1/4). At week 12, 52% of patients were HCV RNA negative and 72% had a >2 log10 decrease in viral load, compared with baseline; 87% and 71% of these patients, respectively, attained an SVR. Therapy was discontinued in 3 patients as a result of adverse events. No patient required ribavirin dose reduction; PEG-IFN-alpha2b dose was reduced in 23% of patients to manage neutropenia. Combination therapy with PEG-IFN-alpha2b and ribavirin treatment was effective in children with chronic hepatitis C. Virologic status at week 12 identified future responders and nonresponders. PEG-IFN-alpha2b and ribavirin were reasonably well tolerated, with no unexpected or permanent adverse effects. Further studies are needed to identify the optimum treatment regimen for this patient population.
    • Treatment decisions of HCV in the pediatric population should consider similar factors as in adulthood. Treatment with pegylated interferon and ribavirin has demonstrated comparable SVR rates of 53% to adults [248][249][250][251]. Although it is anticipated that DAA treatment outcomes will be similar to adults there are currently no safety and efficacy data in the pediatric population.
    [Show abstract] [Hide abstract] ABSTRACT: Background . Hepatitis C virus (HCV) coinfection occurs in 20–30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose . To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods . A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results . The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion . Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.
    Full-text · Article · Jan 2016
    • This retrospective study was performed in a large unique monocentric cohort of 82 pediatric patients infected with difficult-to-treat HCV genotypes 1 and 4, who were treated with peg-IFN and RBV. Up to now, the results of several trials in children and adolescents with chronic hepatitis C using peg-IFNα-2a or 2b in combination with RBV have been reported [13–17]. As expected, based on adult studies, the rates of virological response were significantly lower in patients infected with HCV genotypes 1 and 4 than in patients infected with other genotypes.
    [Show abstract] [Hide abstract] ABSTRACT: IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4. We determined three SNPs of IL-28B (rs12979860, rs12980275, and rs8099917) in 82 patients with chronic HCV infection treated with pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Treatment response and clinical data were analyzed. Overall, sustained virological response (SVR) was achieved by 45 % of patients infected with difficult-to-treat HCV genotypes 1 and 4. Except for IL-28B polymorphisms, there was no association of SVR with any other clinical data. IL-28B rs12979860 CC [odds ratio (OR), 6.81; p = 0.001] and rs8099917 TT (OR, 3.14; p = 0.013) genotypes were associated with higher SVR rates. IL-28B rs12980275 was not significantly associated with SVR (p = 0.058). Only the distribution between CC and CT-TT genotypes of rs12979860 significantly differentiated patients achieving early virological response (EVR) (OR, 10.0; p = 0.011). Children with the rs12979860 CC genotype had significantly higher baseline viral load compared with CT-TT patients (p = 0.010). In children and adolescents chronically infected with HCV genotypes 1 and 4, IL-28B rs12979860 and rs8099917 polymorphisms were the only predictors of response to peg-IFN/RBV.
    Full-text · Article · Jan 2013
    • The current meta-analysis indicates that peg-IFN plus RBV is effective in the majority of children and adolescents with Zhang et al, 2005 [13] No data reported. Jara et al, 2008 [14] 22 of 26 patients experienced an average of 1.6-cm reduction in growth (compared with 50th percentile for age and sex) during the treatment phase. During the 24-week follow-up period, growth velocity was entirely normal.
    [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
    • We were unable to bring out an accurate conclusion about the impact of INF on the impairment of growth velocity, because we had a limited number of children involved in this study. Today there are serious studies that assess the growth of children during the treatment with INF and 5 years later without treatment [29,30].
    [Show abstract] [Hide abstract] ABSTRACT: Treatment of Hepatitis C in children has a better outcome than in adults, and for this reason the treatment had different views. However, in pediatric age hepatitis C is seen to have an evolution towards chronicity. Today is a normal option to treat chronic hepatitis C as early as possible according to certain criteria. The aim of this study is to show the results of treatment with interferon and ribavirin and the follow-up of children diagnosed with chronic hepatitis C in our service. This is a prospective study which has included children 3 up to 15 years old (13 boys and 4 girls) diagnosed with chronic hepatitis C. All patients underwent a certain protocol, including liver biopsy prior to treatment. Treatment consisted in use for 48 weeks of INF α-2b, 3 MIU/m2 three times a week s/c and ribavirin 15 mg/kg orally divided bid. Two patients were treated with PEGINF α-2b with dose 1.5 mcg/kg once a week s/c and ribavirin 15 mg/kg. After the treatment all patients have stayed under our control for an average period of 24 weeks. At the end of the treatment we detected a patient with HCV-RNA positive. End Treatment Viral Response was 94%. Six months later we found three patients who showed relapse of disease. Sustained Viral Response was approximately 83% The combination therapy of interferon with Ribavirin in treatment of children with chronic hepatitis C provides a higher SVR when treatment is initiated at the earliest stages of hepatic changes. Side effects of therapy are insignificant in comparison with results obtained.
    Full-text · Article · Jan 2012
    • The authors do not mention how the infection was acquired. Based on previous experiences [14] [15], patients with genotype 2 or 3 with a low viral load (HCV-RNA less than 600,000 IU/ml) were treated for 24 weeks, whereas children infected with genotype 1 or 4, and genotype 3 with a high viral load (HCV-RNA greater than 600,000 IU/ml) received 48 weeks of therapy. The primary endpoint was a sustained virological response (SVR), defined as the absence of serum HCV-RNA after 24 weeks from therapy; secondary end-points were rapid virological response (RVR), defined as undetectable HCV-RNA at week 4 of treatment, and early virological response (EVR), defined as complete absence of serum HCV-RNA at week 12 of therapy.
    Full-text · Article · Apr 2010
    • Children with verified chronic HCV should be monitored annually for HCV RNA and liver function tests. When considering antiviral therapy, the same contraindications apply for children as for adults [53,54]. Due to the risk of interferon induced growth retardation [55] , treatment is not recommended during periods of intense growth, i.e. before the age of 3 y and during puberty [56] .
    [Show abstract] [Hide abstract] ABSTRACT: In a recent expert meeting, Swedish recommendations for the treatment of HCV infection were upgraded. The panel recommends vaccination against both hepatitis A and B in patients with HCV. Therapy for symptomatic acute HCV infection should be initiated if spontaneous resolution has not occurred within 12 weeks, whereas asymptomatic acute HCV should be treated upon detection. Patients with genotype 2/3 infection should generally be treated for 24 weeks. In patients with a very rapid viral response (vRVR), i.e. HCV RNA below 1000 IU/ml on d 7, treatment can be shortened to 12-16 weeks, provided that no dose reduction has been made. For genotype 1 patients with rapid viral response (RVR), 24 weeks treatment is recommended. For patients with a complete early viral response (cEVR), 48 weeks treatment is recommended, whereas 72 weeks treatment should be considered for patients with partial early viral response (pEVR). For patients with difficult-to-treat disease and with pronounced anaemia, erythropoietin can be used to maintain the ribavirin dose. In HCV-HIV coinfected patients, combination therapy for HCV should, if possible, be initiated before anti-retroviral therapy (ART) is indicated. For liver transplant patients pre-emptive therapy is not recommended; hence, treatment should be deferred until histological recurrence.
    Full-text · Article · Jan 2009
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