The effect of baseline resistance-associated substitutions on the sustained virologic response at 12 weeks in chronic hepatitis C subjects has drawn considerable attention. However, it has been reported that the relationship between such substitutions and sustained virologic response at 12 weeks in chronic hepatitis C subjects is variable in different treatments. This meta-analysis was performed to evaluate this relationship in subjects treated with glecaprevir/pibrentasvir. A systematic literature search up-to May 2020 was done and 17 studies were identified with 6501 chronic hepatitis C subjects. They were reporting relationships between baseline resistance-associated substitutions and sustained virologic response at 12 weeks in chronic hepatitis C subjects treated with glecaprevir/pibrentasvir. The Odds Ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of baseline resistance-associated substitutions on the sustained virologic response at 12 weeks in chronic hepatitis C subjects treated with glecaprevir/pibrentasvir using the dichotomous method with a random or fixed-effect model. Lower sustained virologic response at 12 weeks post treatment in chronic hepatitis C subjects was significantly related to baseline resistance-associated substitutions in overall genotypes (OR, 0.03; 95% CI, 0.15-0.61, p<0.001), baseline NS5a resistance-associated substitutions in genotype-1 (OR, 0.16; 95% CI, 0.04-0.57, p=0.005), baseline resistance-associated substitutions in genotype-3 (OR, 0.14; 95% CI, 0.05-0.38, p<0.001), and baseline NS5a resistance-associated substitutions in genotype-3 (OR, 0.21; 95% CI, 0.09-0.49, p<0.001). Sustained virologic response at 12 weeks in chronic hepatitis C subjects was not significantly related to the baseline NS5a resistance-associated substitutions (OR, 0.61; 95% CI, 0.17-2.22, p=0.45); and baseline resistance-associated substitutions in genotype-1 (OR, 0.35; 95% CI, 0.12-1.088, p=0.07). In conclusion, the impact of baseline resistance-associated substitutions on the sustained virologic response at 12 weeks in chronic hepatitis C subjects treated with glecaprevir/pibrentasvir may have a great prognostic effect, especially in genotype-3 as a tool to improve treatment prediction. Chronic hepatitis C subjects with baseline resistance-associated substitutions may have an independent risk relationship with poor treatment outcomes. This relationship forces us to recommend testing prior to treatment selection to avoid any possible treatment failure.
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