Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience

Clin Transplant. 2017 Nov;31(11). doi: 10.1111/ctr.13109. Epub 2017 Sep 24.

Abstract

The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.

Keywords: asunaprevir; daclatasvir; hepatitis C; liver transplantation.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Carbamates
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Rejection / pathology
  • Graft Survival / drug effects*
  • Hepacivirus / drug effects*
  • Hepatitis C / surgery*
  • Humans
  • Imidazoles / therapeutic use*
  • Isoquinolines / therapeutic use*
  • Japan
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Protease Inhibitors / therapeutic use
  • Pyrrolidines
  • Recurrence
  • Risk Factors
  • Sulfonamides / therapeutic use*
  • Valine / analogs & derivatives

Substances

  • Carbamates
  • Imidazoles
  • Isoquinolines
  • Protease Inhibitors
  • Pyrrolidines
  • Sulfonamides
  • Valine
  • daclatasvir
  • asunaprevir