| Abstract: | 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 < .001), baseline NS5a resistance‐associated substitutions in genotype‐1 (OR, 0.16; 95% CI, 0.04‐0.57, P = .005), baseline resistance‐associated substitutions in genotype‐3 (OR, 0.14; 95% CI, 0.05‐0.38, P < .001), and baseline NS5a resistance‐associated substitutions in genotype‐3 (OR, 0.21; 95% CI, 0.09‐0.49, P < .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 = .45), and baseline resistance‐associated substitutions in genotype‐1 (OR, 0.35; 95% CI, 0.12‐1.088, P = .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. |
