Department of Pharmacy, Ditmanson medical foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan.
Division of Nephrology, Department of Medicine, Zouying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
Ann Med. 2022 Dec;54(1):108-120. doi: 10.1080/07853890.2021.2012589.
Glecaprevir/pibrentasvir (G/P; 300 mg/120 mg) is a new direct-acting antiviral (DAA) that exhibits anti-hepatitis C virus (HCV) pan-genotype (GT) activity for 8, 12, or 16 weeks. However, the U.S. Food and Drug Administration have received reports that using G/P causes moderate to severe liver impairment. In some cases, isolated hyperbilirubinemia and jaundice have been reported without concomitant evidence of increased transaminase levels or other hepatic decompensation events. This study aimed to analyze the incidence of drug-induced liver injury of G/P for chronic hepatitis C virus. We searched databases from the inception of each database until March 2021. Data were pooled using a random-effects model. The Cochrane Risk of Bias Tool (RoB 2.0) and the OpenMeta [Analyst] software were performed for quality assessment and quantitative studies, respectively. The primary outcome was grade 3 level of drug-induced liver injury (DILI). The nine studies included in the meta-analysis involved a total of 7,650 participants, and the overall sustained virologic response rate was above 95%. The most frequent drug-related laboratory abnormalities in DILI involved total bilirubin, alanine aminotransferase, aspartate aminotransferase, and hemoglobin, but these abnormalities were minimal. The cirrhosis-without cirrhosis incidence risk ratio (IRR) was 2.724 (95% confidence interval: 1.182-6.276) in the grade 3 hyperbilirubinemia subgroup analysis. No significant differences were found within the other subgroups, in HCV GTs, and in treatment duration. DILI was found to occur frequently with G/P treatment. Hyperbilirubinemia occurred most frequently, especially, in patients with cirrhosis. However, G/P is still the primary therapy of choice for CKD and end-stage renal disease (ESRD) patients due to a superior safety rate.
格卡瑞韦哌仑他韦（G/P；300mg/120mg）是一种新的直接作用抗病毒药物（DAA），对 8、12 或 16 周的丙型肝炎病毒（HCV）全基因型（GT）均具有抗 HCV 活性。然而，美国食品和药物管理局已收到报告称，使用 G/P 会导致中重度肝损伤。在某些情况下，报告了孤立的高胆红素血症和黄疸，而没有同时伴有转氨酶水平升高或其他肝失代偿事件的证据。本研究旨在分析 G/P 治疗慢性丙型肝炎病毒药物性肝损伤的发生率。我们从每个数据库的创建开始搜索数据库，直到 2021 年 3 月。使用随机效应模型汇总数据。使用 Cochrane 偏倚风险工具（RoB 2.0）和 OpenMeta [Analyst] 软件分别对质量评估和定量研究进行分析。主要结局是 3 级药物性肝损伤（DILI）的发生率。纳入荟萃分析的 9 项研究共涉及 7650 名参与者，总体持续病毒学应答率超过 95%。DILI 中最常见的与药物相关的实验室异常涉及总胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转移酶和血红蛋白，但这些异常是轻微的。在 3 级高胆红素血症亚组分析中，肝硬化无肝硬化发生率风险比（IRR）为 2.724（95%置信区间：1.182-6.276）。在其他亚组、HCV GT 组和治疗持续时间内未发现差异。发现 G/P 治疗时常发生 DILI。高胆红素血症最常发生，特别是在肝硬化患者中。然而，由于安全性更高，G/P 仍然是慢性肾脏病（CKD）和终末期肾病（ESRD）患者的主要治疗选择。
