Comparing Therapeutic Regimens for Pediatric Chronic HCV
Background To decide when and how to treat children with chronic hepatitis C is an ongoing debate.
Aim To compare the outcomes of therapy for children with chronic hepatitis C.
Methods An electronic database assessed clinical trials with sustained virological response rates specified by genotype. The data were extracted according to the therapeutic regimen; interferonα±ribavirin and pegylated interferonα±ribavirin.
Results The search sourced 23 peer-reviewed articles which enrolled 934 cases, aged 2–19 years. Sustained virological response rates were significantly higher with the addition of ribavirin to either interferonα or pegylated nterferonα vs. their monotherapies for genotypes 1,2&3 with crude and weighted estimates. The weighted estimate indicated higher sustained virological response rates for those treated with pegylated interferonα+ribavirin vs. interferonα+ribavirin for genotype 1 (50% vs. 40%) and genotypes 2&3 (90% vs. 84%), (odds ratio 1.5, 95% confidence interval 1.2–1.8, and 1.8, 1.2–2.9 respectively). Cases with genotype 4 treated with pegylated interferonα+ribavirin had a lower sustained virological response (41%) vs. genotype 1 (1.4, 1.2–1.8), and vs. genotypes 2&3 (13.5, 10.3–17.9). Some adverse events were significantly higher among cases treated with pegylated interferonα+ribavirin vs. interferonα+ribavirin.
Conclusions Despite the superiority of pegylated interferonα+ribavirin to interferonα+ribavirin for the treatment of chronic hepatitis C among children, the significant higher adverse events along with the modest outcome for genotypes 1&4 render that regimen a suboptimal therapy. These data indicated the need for the future comparison with clinical trials of direct anti-viral drugs for children with chronic hepatitis C.
Polyethylene glycol (Peg) interferon alpha (IFNα) plus (+) ribavirin (RV) has shown significantly, higher sustained virological response (SVR) compared with IFNα + RV in randomised, controlled studies among adult patients with chronic hepatitis C (CHC). The recommended duration of therapy for CHC among both adults, and children studies is 48 weeks for genotype (G)1&4, and 24 weeks for G2&3.
The slowly progressive, benign course, potential adverse events of the current therapy and variable rates of spontaneous viral clearance of hepatitis C virus (HCV) in children compared with adults, drive some clinicians to defer treatment of CHC among children. However, arguments in favour of treatment of CHC in this population relied on the meta-analyses of early studies of IFNα monotherapy compared with spontaneous viral clearance, which demonstrated significantly better outcome. The lower cost of therapy needed for smaller sized cases compared with adults, fewer comorbid diseases and involvement of parents to ensure adherence of therapy would yield potentially higher response rates.
The benefits of achieving SVR at a young age might offset the possibility of progression to serious chronic liver disease. A study concluded that, it seems reasonable that not all children receive therapy but, rather for only those with more severe liver disease and positive predictive factors for response. Others have suggested that it is difficult to predict which individuals will progress to more serious liver disease, since risk factors associated with the disease progression in this population are not fully evaluated.
The Food and Drug Administration licenced IFNα2b + RV, PegIFNα2b and PegIFNα2a for the treatment of children and adolescents with CHC in 2002, 2008 and 2009 respectively. In the absence of randomised, controlled studies among children to compare the outcome of these regimens, it is not be feasible to adopt an evidence-based assumption for the ideal therapeutic regimen. Despite the publication of two systematic reviews among children treated for CHC, the authors neither conducted a comparison of the weighted SVR with the therapeutic regimens, nor an assessment according to the HCV genotype.
Hence, this systematic review aimed to compare the SVR among children treated for CHC according to the HCV genotype with different therapeutic regimens (IFNα ± RV and PegIFNα ± RV) using combined tests of statistical analysis. The conclusions drawn from evidence-based data regarding the efficacy and the safety of each regimen might support the future management of CHC among that cohort.
Abstract and Introduction
Abstract
Background To decide when and how to treat children with chronic hepatitis C is an ongoing debate.
Aim To compare the outcomes of therapy for children with chronic hepatitis C.
Methods An electronic database assessed clinical trials with sustained virological response rates specified by genotype. The data were extracted according to the therapeutic regimen; interferonα±ribavirin and pegylated interferonα±ribavirin.
Results The search sourced 23 peer-reviewed articles which enrolled 934 cases, aged 2–19 years. Sustained virological response rates were significantly higher with the addition of ribavirin to either interferonα or pegylated nterferonα vs. their monotherapies for genotypes 1,2&3 with crude and weighted estimates. The weighted estimate indicated higher sustained virological response rates for those treated with pegylated interferonα+ribavirin vs. interferonα+ribavirin for genotype 1 (50% vs. 40%) and genotypes 2&3 (90% vs. 84%), (odds ratio 1.5, 95% confidence interval 1.2–1.8, and 1.8, 1.2–2.9 respectively). Cases with genotype 4 treated with pegylated interferonα+ribavirin had a lower sustained virological response (41%) vs. genotype 1 (1.4, 1.2–1.8), and vs. genotypes 2&3 (13.5, 10.3–17.9). Some adverse events were significantly higher among cases treated with pegylated interferonα+ribavirin vs. interferonα+ribavirin.
Conclusions Despite the superiority of pegylated interferonα+ribavirin to interferonα+ribavirin for the treatment of chronic hepatitis C among children, the significant higher adverse events along with the modest outcome for genotypes 1&4 render that regimen a suboptimal therapy. These data indicated the need for the future comparison with clinical trials of direct anti-viral drugs for children with chronic hepatitis C.
Introduction
Polyethylene glycol (Peg) interferon alpha (IFNα) plus (+) ribavirin (RV) has shown significantly, higher sustained virological response (SVR) compared with IFNα + RV in randomised, controlled studies among adult patients with chronic hepatitis C (CHC). The recommended duration of therapy for CHC among both adults, and children studies is 48 weeks for genotype (G)1&4, and 24 weeks for G2&3.
The slowly progressive, benign course, potential adverse events of the current therapy and variable rates of spontaneous viral clearance of hepatitis C virus (HCV) in children compared with adults, drive some clinicians to defer treatment of CHC among children. However, arguments in favour of treatment of CHC in this population relied on the meta-analyses of early studies of IFNα monotherapy compared with spontaneous viral clearance, which demonstrated significantly better outcome. The lower cost of therapy needed for smaller sized cases compared with adults, fewer comorbid diseases and involvement of parents to ensure adherence of therapy would yield potentially higher response rates.
The benefits of achieving SVR at a young age might offset the possibility of progression to serious chronic liver disease. A study concluded that, it seems reasonable that not all children receive therapy but, rather for only those with more severe liver disease and positive predictive factors for response. Others have suggested that it is difficult to predict which individuals will progress to more serious liver disease, since risk factors associated with the disease progression in this population are not fully evaluated.
The Food and Drug Administration licenced IFNα2b + RV, PegIFNα2b and PegIFNα2a for the treatment of children and adolescents with CHC in 2002, 2008 and 2009 respectively. In the absence of randomised, controlled studies among children to compare the outcome of these regimens, it is not be feasible to adopt an evidence-based assumption for the ideal therapeutic regimen. Despite the publication of two systematic reviews among children treated for CHC, the authors neither conducted a comparison of the weighted SVR with the therapeutic regimens, nor an assessment according to the HCV genotype.
Hence, this systematic review aimed to compare the SVR among children treated for CHC according to the HCV genotype with different therapeutic regimens (IFNα ± RV and PegIFNα ± RV) using combined tests of statistical analysis. The conclusions drawn from evidence-based data regarding the efficacy and the safety of each regimen might support the future management of CHC among that cohort.
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