Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study

Abstract

Abbreviations: AE, adverse event; ALT, alanine aminotransferase; APaT, all participants as treated; APRI, aspartate aminotransferase to platelet ratio index; ART, antiretroviral therapy; AST, aspartate aminotransferase; DAA, direct-acting antiviral; EBR/GZR, elbasvir/grazoprevir; FAS, full analysis set; GT, genotype; HBsAg, hepatitis B surface antigen; LLOQ, lower limit of quantification; mFAS, modified full analysis set; NS5A, non-structural protein 5A; RAS, resistance-associated substitutions; SVR, sustained virologic response; SVR12, sustained virologic response at 12 weeks after the completion of all study therapy. Abstract Background & Aims: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub-Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection. Methods: In this partially randomized, open-label multicentre study conducted in France (NCT03111108; Protocol MK5172-096), treatment-naive participants with | 1043 ASSELAH Et AL. 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy. Results: One hundred and seventeen participants were enrolled. Among treatmentnaive participants with F0-F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12-week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance-associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug-related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event. Conclusion: These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment-experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment-naive individuals with mild fibrosis can be treated effectively with an 8-week regimen. K E Y W O R D S hepatitis C, randomized controlled trial, therapeutics Key points • The combination of two drugs, elbasvir and grazoprevir, was effective in treating hepatitis C virus genotype 4 infection.• Some individuals require these medicines once daily for 12 weeks to achieve a cure, whereas many of those who have not been treated previously and have mild liver disease can achieve cure after treatment for 8 weeks. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Asselah T, Pol S, Hezode C, et al. Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study.

Phase 3, Multicenter Open‐Label study to investigate the efficacy of elbasvir and grazoprevir fixed‐dose combination for 8 weeks in treatment‐naïve, HCV GT1b‐infected patients, with non‐severe fibrosis

“…Similarly, in a partially randomized, open‐label multicenter study conducted in France (NCT03111108), GT4 treatment‐naive individuals with mild fibrosis can also be treated effectively with an 8‐week regimen 34 …”

Quantitative and qualitative lipid improvement with chronic hepatitis C virus eradication using direct‐acting antivirals

“…1 Direct-acting antivirals (DAAs) have revolutionized HCV therapy, with sustained virological response (SVR) rates of over 95% for the most common genotypes regardless of comorbidities. [2][3][4][5][6] The achievement of an SVR by DAAs in patients with chronic HCV infection also implies substantial improvements in liver histological findings, liver function, gastroesophageal varices grades, HCC complication risk, and more in the clinical setting. [7][8][9] HCV hijacks hepatic lipid pathways in multiple aspects of its life cycle, starting with attachment of the HCV particle to lowdensity lipoprotein (LDL) and high-density lipoprotein (HDL) receptors of scavenger receptor class B type 1 and ensuing expression regulation, [10][11][12] all of which suggest a close association between HCV infection and serum lipid levels.…”

Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM

“…In chronic HCV infection, the C-WORTHY trial showed that higher SVR12 rates were achieved in patients treated with 12-week versus 8-week grazoprevir/elbasvir. 17 Nevertheless, more recent clinical trials evaluating 8-week grazoprevir/elbasvir have demonstrated high SVR in HCV genotype 1b or 4 infected patients with liver fibrosis levels at METAVIR F0-F2 25,26 or in genotype 1b when plasma HCV-RNA is low. 27 Given that MSM recently acquiring HCV are unlikely to have severe liver fibrosis 28 , 8-week duration of grazoprevir/elbasvir could be sufficient for treating acute HCV.…”