Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Patients With Previous Direct-Acting Antiviral Therapy Failures: A Meta-Analysis

Abstract

Background: Since a greater number of hepatitis C virus (HCV) patients have access to direct-acting antiviral (DAA) based therapies, the number of patients not properly responding to prior DAA regimens is increasing. The objective of this comprehensive analysis was to assess the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in HCV patients who experienced previous DAA therapy failures.Methods: Bibliographic databases were systematically searched for relevant articles published by November 2020. The main endpoints were sustained viral response after 12 weeks (SVR12), adverse events (AEs; any grade) and severe adverse events (SAEs). Publication bias assessment was performed using funnel plots and the Egger's test.Results: Fourteen studies consisting of a total of 1,294 subjects were included in this study and the pooled estimate of SVR12, AEs and SAEs rates were 96.8% (95%CI: 95.1–98.2), 47.1% (95%CI: 26.0–69.3), and 1.8% (95%CI: 0.7–3.4), respectively. Subgroup analysis showed that pooled SVR12 rates were 97.9% (95%CI: 96.7–98.9) for Japan and 91.1% (95%CI: 87.3–94.3) for the United States; 95.8% (95%CI: 93.9–97.4) for genotype (GT)1 and 100.0% (95%CI: 99.6–100.0) for GT2; 95.3% (95%CI: 92.4–97.2) for cirrhosis and 96.3% (95%CI: 94.2–97.7) for non-cirrhosis cases. There was no publication bias included this study.Conclusion: This comprehensive analysis revealed that GLE/PIB is an effective and secure retreatment option for patients who did not optimally respond to DAA treatment, especially the Asian population with GT1-2.

Next-generation sequencing analysis of hepatitis C virus resistance–associated substitutions in direct-acting antiviral failure in South Korea

“…Treatment with GLE/PIB was highly effective in patients with GT 2 infection who experienced failure in SOF+RBV showing 100% of SVR rate and is currently recommended for patients with sofosbuvir failure. 35 In our study, GLE/PIB was also highly effective in patients with GT 2 infection and failure of SOF+RBV therapy.…”

Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens

“…The treatment time, in accordance with the National Health Fund program, was 12 weeks, which diverts from the AASLD guidelines recommending 16-week therapy. However, the available data from the meta-analysis by Shen et al, summarizing the effectiveness and safety of GLE/PIB in patients with a history of ineffective DAA therapy, documents the lack of statistically significant difference in virological response for 12- and 16-week treatment with an overall SVR of 96.8% [ 27 ]. Most of the reports included in this meta-analysis were carried out in the Japanese population, with only two studies (two out of the three with a 16-week duration) with a total of 268 patients being from the U.S., with an SVR lower by 6.8% (91.1 vs. 97.9%).…”

“…The most frequent factor associated with the failure of antiviral therapy is liver cirrhosis, especially in the case of decompensation [ 29 ]. Although this is denied by the meta-analysis by Shen et al regarding GLE/PIB therapy (SVR 95.3% with cirrhosis and 96.3% with non-cirrhosis), many researchers are in agreement regarding this issue [ 27 , 30 ]. This is also confirmed by the current analysis.…”

“…The profile and percentage of adverse effects occurring in the group treated by us varies slightly from those reported by other researchers. The total number of patients reporting adverse effects is lower (23.3% vs. >40%), which could be the result of not reporting the less inconvenient effects [ 27 , 28 , 32 ]. The most common adverse event, reported by 10% of patients, was fatigue.…”

Early post‐liver transplant use of direct‐acting antivirals in naive and NS5A inhibitor‐experienced HCV patients

“…A huge amount of data about the efficacy and safety of DAAs in HCV population are now available, with an overall sustained viral response rate after 12 weeks from the end of therapy (SVR12) above 95% 6–10 . However, in patients with decompensated cirrhosis and/or active hepatocellular carcinoma (HCC) SVR12 rates are lower, around 80–90% 11–13 .…”