The Efficacy of Daclatasvir Plus Asunaprevir Combination Therapy with Chronic Hepatitis

  • Fukiko MitsuiEmail author
  • C. Nelson Hayes
  • Fumitaka Suzuki
  • Kazuaki Chayama


In late years, therapeutic drugs for hepatitis C virus (HCV) have made impressive progress. In particular, the introduction of direct-acting antiviral agents (DAAs), which target viral proteins directly, has advanced the treatment of HCV with high sustained virological response (SVR) rates and few side effects. Despite their potency, monotherapy with a single agent is not effective due to rapid selection for strains harboring resistance-associated variants (RAVs). However, when DAAs with different mechanisms of action are used together, they present a high genetic barrier to resistance and have been shown to be effective for treatment of patients with HCV genotype 1, including patients who are poor candidates for interferon therapy and patients who failed to respond to previous treatment attempts. In a phase 3 trial examining 24 weeks of dual DAA therapy with asunaprevir, an NS3 protease inhibitor, and daclatasvir, an NS5A replication complex inhibitor, in Japanese patients infected with HCV genotype 1 with a high HCV RNA titer, the SVR rate reached 81–91 %. Moreover, 94–100 % of patients without NS5A L31 and/or Y93 or NS3 D168 RAVs at baseline achieved SVR. The rate of adverse events was low, and this combination therapy was well tolerated. However, attention should be paid to AST/ALT elevation, pyrexia, and rash. Patients with cirrhosis are eligible for this therapy, but it is necessary to manage side effects carefully with consideration for the general condition of the patient. It is important to provide the best treatment currently available in the treatment of aging Japanese patients with hepatitis C to suppress progression of liver disease and reduce risk of hepatocellular carcinoma.


Daclatasvir Asunaprevir IFN-free Direct-acting antiviral agents (DAAs) 


  1. 1.
    Yamada I, Suzuki F, Kamiya N, Aoki K, Sakurai Y, Kano M, Matsui H, Kumada H. Safety, pharmacokinetics and resistant variants of telaprevir alone for 12 weeks in hepatitis c virus genotype 1b infection. J Viral Hepat. 2012;19:e112–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Toyota J, Ozeki I, Karino Y, Asahina Y, Izumi N, Takahashi S, Kawakami Y, Chayama K, Kamiya N, Aoki K, et al. Virological response and safety of 24-week telaprevir alone in japanese patients infected with hepatitis c virus subtype 1b. J Viral Hepat. 2013;20:167–73.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, Serrano-Wu MH, Langley DR, Sun JH, O’Boyle 2nd DR, et al. Chemical genetics strategy identifies an hcv ns5a inhibitor with a potent clinical effect. Nature. 2010;465:96–100.CrossRefPubMedGoogle Scholar
  4. 4.
    Chayama K, Takahashi S, Toyota J, Karino Y, Ikeda K, Ishikawa H, Watanabe H, McPhee F, Hughes E, Kumada H. Dual therapy with the nonstructural protein 5a inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis c virus genotype 1b-infected null responders. Hepatology. 2012;55:742–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Suzuki Y, Ikeda K, Suzuki F, Toyota J, Karino Y, Chayama K, Kawakami Y, Ishikawa H, Watanabe H, Hu W, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with hcv genotype 1b infection and limited treatment options. J Hepatol. 2013;58:655–62.CrossRefPubMedGoogle Scholar
  6. 6.
    Karino Y, Toyota J, Ikeda K, Suzuki F, Chayama K, Kawakami Y, Ishikawa H, Watanabe H, Hernandez D, Yu F, et al. Characterization of virologic escape in hepatitis c virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir. J Hepatol. 2013;58:646–54.CrossRefPubMedGoogle Scholar
  7. 7.
    Kumada H, Suzuki Y, Ikeda K, Toyota J, Karino Y, Chayama K, Kawakami Y, Ido A, Yamamoto K, Takaguchi K, et al. Daclatasvir plus asunaprevir for chronic hcv genotype 1b infection. Hepatology. 2014;59:2083–91.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2017

Authors and Affiliations

  • Fukiko Mitsui
    • 1
    Email author
  • C. Nelson Hayes
    • 1
    • 2
  • Fumitaka Suzuki
    • 3
  • Kazuaki Chayama
    • 1
    • 2
    • 4
  1. 1.Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Liver Research Project CenterHiroshima UniversityHiroshimaJapan
  3. 3.Department of HepatologyToranomon HospitalTokyoJapan
  4. 4.Laboratory for Digestive DiseasesCenter for Genomic Medicine, RIKENHiroshimaJapan

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