Comparing Therapeutic Regimens for Pediatric Chronic HCV
Comparing Therapeutic Regimens for Pediatric Chronic HCV
An electronic database search was conducted in PubMed, SCOPUS, EBSCO and Cochrane Library websites using key words; children, CHC, treatment, IFN, PegIFN. No restriction of language, study design, sample size or the outcome of each study was set. Peer-reviewed articles were targeted without screening for relevant abstracts.
Clinical trials among cases treated for CHC were selected for; SVR report (undetectable HCV RNA in the blood, normal alanine aminotransferase 24 weeks post-treatment), specified by the HCV genotype, age ≤18 years, from January 1990 to November 2014, and full data of the used regimen. Other outcome variables including: breakthrough (recurrence of HCV RNA during treatment after an initial loss), relapse (recurrence of HCV RNA after being negative at the end of treatment) and adverse events; were optional and quoted wherever explicitly reported.
Exclusion criteria consisted of: SVR not reported or not specified by the genotype, irrelevant concept, treatment course <48 weeks, except for G2&3, review articles, case reports, presence of hepatitis B virus or Human immune deficiency virus co-infection, comorbid disorders or previous anti-viral therapy of ≥50% among the treated children, and potential duplication.
The study eligibility depended on inclusion and exclusion criteria. Along these studies, cases were assigned according to the therapeutic regimen (including case–control trials) to make appropriate comparisons. Such attempts were justified by the low degree of heterogeneity in the childhood period compared with adults regarding; age, duration of infection, CHC pathology, associated comorbid disorders and the rate of previous anti-HCV therapy, which might constitute potential confounders.
The data were extracted from the original articles by two authors independently; any discrepancy was discussed and resolved. Extraction of data was done according to the treatment policy, and manually tabulated in crude numbers and percentages. Comparisons were conducted between groups according to the regimen used for the pooled data (group IFNα, group IFNα + RV, group PegIFNα and group PegIFNα + RV). Assessments were set for; (i) therapeutic outcomes: SVR according to HCV genotype, breakthrough, relapse; (ii) comorbid diseases with CHC (data in items 1,2 were evaluated among the four groups); (iii) adverse events (among those treated with both combined regimens).
The primary therapeutic endpoint, i.e. SVR was expressed according to HCV genotype in each study as a crude proportion [number of children achieved SVR/total number of treated cases 'n'], as well as a weighted proportion [weight of each study multiplied by SVR crude proportion]. The study weight was estimated by inverse of the variance, which was released by the formula: SVR crude proportion multiplied by [1–SVR crude proportion]/n.
Comparisons were conducted for the SVR crude estimate [Σ crude proportions (i)/Σ n (i)] and for the SVR weighted estimate [Σ weighted proportions (i)/Σ studies' weights (i)], where i = study 1 + study 2, etc., in each group as mentioned before.
Wherever significant (<0.05), the probability (P) value was given for the crude estimate, while the weighted estimate was expressed by odds ratio (OR) and its 95% confidence interval (CI). Epi Info software, 2002 (CDC, Atlanta, GA, USA) was used to compare the outcome of treatment and adverse events among the groups through the Mantel–Haenszel test.
Methods
Search Strategy
An electronic database search was conducted in PubMed, SCOPUS, EBSCO and Cochrane Library websites using key words; children, CHC, treatment, IFN, PegIFN. No restriction of language, study design, sample size or the outcome of each study was set. Peer-reviewed articles were targeted without screening for relevant abstracts.
Inclusion Criteria
Clinical trials among cases treated for CHC were selected for; SVR report (undetectable HCV RNA in the blood, normal alanine aminotransferase 24 weeks post-treatment), specified by the HCV genotype, age ≤18 years, from January 1990 to November 2014, and full data of the used regimen. Other outcome variables including: breakthrough (recurrence of HCV RNA during treatment after an initial loss), relapse (recurrence of HCV RNA after being negative at the end of treatment) and adverse events; were optional and quoted wherever explicitly reported.
Exclusion Criteria
Exclusion criteria consisted of: SVR not reported or not specified by the genotype, irrelevant concept, treatment course <48 weeks, except for G2&3, review articles, case reports, presence of hepatitis B virus or Human immune deficiency virus co-infection, comorbid disorders or previous anti-viral therapy of ≥50% among the treated children, and potential duplication.
Study Eligibility
The study eligibility depended on inclusion and exclusion criteria. Along these studies, cases were assigned according to the therapeutic regimen (including case–control trials) to make appropriate comparisons. Such attempts were justified by the low degree of heterogeneity in the childhood period compared with adults regarding; age, duration of infection, CHC pathology, associated comorbid disorders and the rate of previous anti-HCV therapy, which might constitute potential confounders.
Data Extraction
The data were extracted from the original articles by two authors independently; any discrepancy was discussed and resolved. Extraction of data was done according to the treatment policy, and manually tabulated in crude numbers and percentages. Comparisons were conducted between groups according to the regimen used for the pooled data (group IFNα, group IFNα + RV, group PegIFNα and group PegIFNα + RV). Assessments were set for; (i) therapeutic outcomes: SVR according to HCV genotype, breakthrough, relapse; (ii) comorbid diseases with CHC (data in items 1,2 were evaluated among the four groups); (iii) adverse events (among those treated with both combined regimens).
Statistical Analysis
The primary therapeutic endpoint, i.e. SVR was expressed according to HCV genotype in each study as a crude proportion [number of children achieved SVR/total number of treated cases 'n'], as well as a weighted proportion [weight of each study multiplied by SVR crude proportion]. The study weight was estimated by inverse of the variance, which was released by the formula: SVR crude proportion multiplied by [1–SVR crude proportion]/n.
Comparisons were conducted for the SVR crude estimate [Σ crude proportions (i)/Σ n (i)] and for the SVR weighted estimate [Σ weighted proportions (i)/Σ studies' weights (i)], where i = study 1 + study 2, etc., in each group as mentioned before.
Wherever significant (<0.05), the probability (P) value was given for the crude estimate, while the weighted estimate was expressed by odds ratio (OR) and its 95% confidence interval (CI). Epi Info software, 2002 (CDC, Atlanta, GA, USA) was used to compare the outcome of treatment and adverse events among the groups through the Mantel–Haenszel test.
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