Real-life glecaprevir/pibrentasvir in a large cohort of patients with hepatitis C virus infection: The MISTRAL study

Liver Int. 2019 Oct;39(10):1852-1859. doi: 10.1111/liv.14170. Epub 2019 Jul 2.

Abstract

Background and aims: It is paramount to identify predictors of treatment failure with direct antiviral agents in 'field-practice' patients, including people who inject drugs (PWID). Data on the efficacy of glecaprevir/pibrentasvir (GLE/PIB) in a field-practice scenario are scant. The multicentre MISTRAL study enrolled 1177 patients, including PWID, to assess real-life efficacy and safety of GLE/PIB and to identify the predictive factors for this treatment.

Methods: This was a prospective, longitudinal study. The outcome variable was the rate of sustained virological response (SVR) at week 12.

Results: A total of 123 patients (10%) were infected from hepatitis C virus (HCV) 3. METAVIR fibrosis score was F4 in 104 subjects (9%); 118 patients (10%) were PWID. Overall, 1163/1177 (99%) patients achieved SVR. The baseline clinical factors discriminating between treatment success and treatment failure were age at treatment (P = 0.031) and creatinine level (P = 0.034). SVR rates were not influenced by gender, substance abuse, previous treatment, treatment duration, fibrosis or chronic kidney disease stage. Compared with non-substance users, the 118 PWID exhibited a significantly different genotype pattern distribution (χ2 < 0.001). A total of 40/118 (33.9%) of substance users were HCV3 compared to 83/1056 (7.9%) non-substance users. Only 6 patients (0.5%) reported a serious adverse event.

Conclusions: The MISTRAL study provides evidence of GLE/PIB efficacy in a field-practice scenario in a highly epidemic HCV area in southern Italy; it unveiled significant differences in genotype distribution among the most underserved and difficult-to-treat patient subgroups including PWID.

Keywords: HCV genotype; cirrhosis; direct-acting antiviral; efficacy; substance abuse.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminoisobutyric Acids
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Italy
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Liver Cirrhosis / virology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Prospective Studies
  • Pyrrolidines
  • Quinoxalines / therapeutic use*
  • Substance Abuse, Intravenous / complications
  • Sulfonamides / therapeutic use*
  • Sustained Virologic Response
  • Young Adult

Substances

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Benzimidazoles
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • pibrentasvir
  • Proline
  • Leucine
  • glecaprevir