Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy

  • Goki Suda
  • Koji Ogawa
  • Yoshiya Yamamoto
  • Masaki Katagiri
  • Ken Furuya
  • Kenichi Kumagai
  • Jun Konno
  • Megumi Kimura
  • Naoki Kawagishi
  • Masatsugu Ohara
  • Machiko Umemura
  • Jun Ito
  • Takaaki Izumi
  • Masato Nakai
  • Takuya Sho
  • Mitsuteru Natsuizaka
  • Kenichi Morikawa
  • Akihito Tsubota
  • Noritomo Shimada
  • Etsuko Iio
  • Yasuhito Tanaka
  • Naoya Sakamoto
  • NORTE Study Group
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy.

Methods

This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12 weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated.

Results

Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7% (13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.

Conclusions

This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.

Keywords

Hepatitis C virus Direct-acting antivirals Retreatment Daclatasvir Sofosbuvir 

Abbreviations

DAAs

Direct-acting antivirals

HCV

Hepatitis C virus

PI

Protease inhibitor

RAVs

Resistance-associated variants

SVR

Sustained virological response

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Copyright information

© Japanese Society of Gastroenterology 2017

Authors and Affiliations

  • Goki Suda
    • 1
  • Koji Ogawa
    • 1
  • Yoshiya Yamamoto
    • 2
  • Masaki Katagiri
    • 3
  • Ken Furuya
    • 4
  • Kenichi Kumagai
    • 5
  • Jun Konno
    • 6
  • Megumi Kimura
    • 1
  • Naoki Kawagishi
    • 1
  • Masatsugu Ohara
    • 1
  • Machiko Umemura
    • 1
  • Jun Ito
    • 1
  • Takaaki Izumi
    • 1
  • Masato Nakai
    • 1
  • Takuya Sho
    • 1
  • Mitsuteru Natsuizaka
    • 1
  • Kenichi Morikawa
    • 1
  • Akihito Tsubota
    • 7
  • Noritomo Shimada
    • 8
  • Etsuko Iio
    • 9
  • Yasuhito Tanaka
    • 9
  • Naoya Sakamoto
    • 1
  • NORTE Study Group
  1. 1.Department of Gastroenterology and Hepatology, Graduate School of MedicineHokkaido UniversitySapporoJapan
  2. 2.Hakodate City General HospitalHakodateJapan
  3. 3.Sapporo Hokuyu HospitalSapporoJapan
  4. 4.JCHO Hokkaido HospitalSapporoJapan
  5. 5.Mori City National Health Insurance HospitalMoriJapan
  6. 6.Hakodate Central General HospitalHakodateJapan
  7. 7.Core Research Facilities for Basic Science, Division of Molecular Cell Biology, Research Center for Medical ScienceThe Jikei University School of MedicineTokyoJapan
  8. 8.Division of Gastroenterology and HepatologyOotakanomori HospitalChibaJapan
  9. 9.Nagoya City University Graduate School of Medical SciencesNagoyaJapan

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