The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world: a comprehensive analysis of a prospective multicenter study

Hepatol Int. 2020 Mar;14(2):225-238. doi: 10.1007/s12072-020-10019-z. Epub 2020 Mar 3.

Abstract

Background: Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment.

Methods: In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed.

Results: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10-5; genotype 2 vs. 3, p = 3.28 × 10-5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10-5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10-5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10-18) patients.

Conclusions: G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.

Keywords: Chronic hepatitis C; Glecaprevir; Multicenter study; Pibrentasvir; Refractory factors.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / therapeutic use*
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / therapeutic use*
  • Quinoxalines / administration & dosage
  • Quinoxalines / therapeutic use*
  • Sulfonamides / administration & dosage
  • Sulfonamides / therapeutic use*
  • Sustained Virologic Response
  • Young Adult

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Drug Combinations
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • glecaprevir and pibrentasvir