Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China.
J Viral Hepat. 2021 Jan;28(1):177-185. doi: 10.1111/jvh.13409. Epub 2020 Oct 13.
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.
基线耐药相关替换对慢性丙型肝炎患者 12 周持续病毒学应答的影响引起了广泛关注。然而，据报道，在不同治疗中，这些替换与慢性丙型肝炎患者 12 周持续病毒学应答之间的关系是可变的。本荟萃分析旨在评估在使用 glecaprevir/pibrentasvir 治疗的患者中这种关系。对截至 2020 年 5 月的系统文献检索确定了 17 项研究，其中包括 6501 例慢性丙型肝炎患者。这些研究报告了基线耐药相关替换与使用 glecaprevir/pibrentasvir 治疗的慢性丙型肝炎患者 12 周持续病毒学应答之间的关系。使用二项分类方法，采用随机或固定效应模型，计算优势比（OR）及其 95%置信区间（CI），以评估基线耐药相关替换对慢性丙型肝炎患者 12 周持续病毒学应答的预后作用。总体基因型（OR，0.03；95%CI，0.15-0.61，P<.001）、基因型 1 基线 NS5a 耐药相关替换（OR，0.16；95%CI，0.04-0.57，P=0.005）、基因型 3 基线耐药相关替换（OR，0.14；95%CI，0.05-0.38，P<.001）和基因型 3 基线 NS5a 耐药相关替换（OR，0.21；95%CI，0.09-0.49，P<.001）与慢性丙型肝炎患者 12 周时持续病毒学应答较低显著相关。慢性丙型肝炎患者 12 周时持续病毒学应答与基线 NS5a 耐药相关替换（OR，0.61；95%CI，0.17-2.22，P=0.45）和基因型 1 基线耐药相关替换（OR，0.35；95%CI，0.12-1.088，P=0.07）无显著相关性。总之，glecaprevir/pibrentasvir 治疗的慢性丙型肝炎患者基线耐药相关替换对 12 周持续病毒学应答的影响可能具有重要的预后作用，尤其是在基因型 3 中，作为改善治疗预测的工具。具有基线耐药相关替换的慢性丙型肝炎患者可能与较差的治疗结局存在独立的风险关系。这种关系迫使我们建议在治疗选择之前进行检测，以避免任何可能的治疗失败。
