Grazoprevir/Elbasvir Treatment in Liver or Kidney Transplant Recipients with Genotype 1b Hepatitis C Virus Infection

Abstract

More options regarding the choice of direct-acting antivirals (DAAs) are helpful for avoiding individual limitations in treating hepatitis C virus (HCV) infection. We aimed to assess the efficacy and tolerability of grazoprevir (GZR)/elbasvir (EBR) treatment in genotype-1b (GT-1b) HCV-infected liver or kidney transplant recipients. In this phase 4, single-arm, open-label, multicenter trial, patients received GZR 100 mg/EBR 50 mg daily for 12 weeks. Patients with any HCV infection other than GT-1b, liver decompensation, human immunodeficiency virus, or hepatitis B virus co-infection, a history of NS5A inhibitor exposure, or any severe drug-drug interactions (DDIs), was excluded. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Of the 14 patients (10 kidney and 4 liver transplant subjects) enrolled in this study, 9 (64%) were females; the median age was 64.0 (range: 43-73) years. The regularly used immunosuppressants were tacrolimus (93%), everolimus (29%), and sirolimus (7%), with patient blood levels easily managed and generally stable (all P > 0.05 in quantile regression analysis). The rate of SVR12 was 100% in intent-to-treat analysis. Only one patient discontinued GZR/EBR therapy at 6 weeks posttreatment, due to a treatment-unrelated adverse event (AE); however, this patient remained, achieving SVR12. Most AEs were mild in severity and deemed to be not treatment-related. No organ rejection episodes or deaths occurred during the study period. The single-tablet regimen of GZR/EBR for 12 weeks is highly effective and well tolerated in GT-1b HCV-infected liver or kidney transplant recipients, and its DDIs are generally easy to manage. (This study has been registered at ClinicalTrials.gov under identifier NCT03723824.).

Keywords: antivirals; chronic hepatitis C; chronic kidney disease; everolimus; immunosuppressant; interaction; protease inhibitor; sirolimus; tacrolimus; transplantation.

Conflict of interest statement

The authors declare a conflict of interest. S.Y. received lecture fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Ipsen, Lilly, and Merck Sharp & Dohme, and served as an advisory board member for AbbVie, Roche, and Ipsen. T.L. received grants from Merck Sharp & Dohme and Gilead Sciences, and served as an advisory board member for Gilead and Bristol-Myers Squibb.

Figures

FIG 1

The changes in blood levels during grazoprevir/elbasvir treatment in quantile regression analysis: (A) alanine aminotransferase; (B) bilirubin; (C) creatinine.

FIG 2

The changes in immunosuppressant blood levels in quantile regression analysis: (A) tacrolimus; (B) everolimus; (C) sirolimus.

FIG 3

The changes in immunosuppressant dosage in quantile regression analysis: (A) tacrolimus; (B) everolimus; (C) sirolimus.