Real-World Experiences with the Combination Treatment of Ledipasvir Plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon Plus Ribavirin with HCV...

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Apr 26

PMID 28441362

Citations 16

Authors

Tatsuo Kanda

Shin Yasui

Masato Nakamura

Eiichiro Suzuki

Makoto Arai

Yoshihiko Ooka

Sadahisa Ogasawara

Tetsuhiro Chiba

Tomoko Saito

Yuki Haga

Koji Takahashi

Reina Sasaki

Shuang Wu

Shingo Nakamoto

Akinobu Tawada

Hitoshi Maruyama

Fumio Imazeki

Naoya Kato

Osamu Yokosuka

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events.

Citing Articles

Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance.

Masaoka R, Gyotoku Y, Shirahashi R, Suda T, Tamano M World J Clin Cases. 2023; 11(22):5204-5214.

PMID: 37621583 PMC: 10445062. DOI: 10.12998/wjcc.v11.i22.5204.

Chronic Hepatitis C: Acute Exacerbation and Alanine Aminotransferase Flare.

Kanda T, Matsumoto N, Ishii T, Arima S, Shibuya S, Honda M Viruses. 2023; 15(1).

PMID: 36680223 PMC: 9861769. DOI: 10.3390/v15010183.

Ledipasvir/Sofosbuvir Is Effective for Relapsed Genotype 1b Hepatitis C Virus Patients after Achieving a Sustained Virological Response at Post-treatment Week 12 with Glecaprevir/Pibrentasvir.

Manabe T, Tadokoro T, Nakahara M, Ohura K, Fujita K, Tani J Intern Med. 2022; 62(17):2507-2511.

PMID: 36450472 PMC: 10518557. DOI: 10.2169/internalmedicine.0865-22.

Efficacy of Glecaprevir/Pibrentasvir for Real-World HCV Infected Patients in the Northern Part of Tokyo, Japan.

Yamana Y, Kanda T, Matsumoto N, Honda M, Kumagawa M, Sasaki R J Clin Med. 2021; 10(23).

PMID: 34884231 PMC: 8658140. DOI: 10.3390/jcm10235529.

MicroRNA-122 as a diagnostic biomarker for hepatocellular carcinoma related to hepatitis C virus: a meta-analysis and systematic review.

Wei X, Ding J, Tian W, Yu Y J Int Med Res. 2020; 48(8):300060520941634.

PMID: 32790532 PMC: 7543180. DOI: 10.1177/0300060520941634.

References

Afdhal N, Reddy K, Nelson D, Lawitz E, Gordon S, Schiff E . Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014; 370(16):1483-93. DOI: 10.1056/NEJMoa1316366. View

. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol. 2016; 66(1):153-194. DOI: 10.1016/j.jhep.2016.09.001. View

Tateishi R, Okanoue T, Fujiwara N, Okita K, Kiyosawa K, Omata M . Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study. J Gastroenterol. 2014; 50(3):350-60. PMC: 4352653. DOI: 10.1007/s00535-014-0973-8. View

Miyauchi T, Kanda T, Imazeki F, Mikata R, Tawada A, Arai M . Response to peginterferon-alpha 2b and ribavirin in Japanese patients with chronic hepatitis C genotype 1. Hepatol Int. 2015; 7(1):144-52. DOI: 10.1007/s12072-012-9349-4. View

Iio E, Shimada N, Abe H, Atsukawa M, Yoshizawa K, Takaguchi K . Efficacy of daclatasvir/asunaprevir according to resistance-associated variants in chronic hepatitis C with genotype 1. J Gastroenterol. 2016; 52(1):94-103. DOI: 10.1007/s00535-016-1225-x. View

Noda I, Kitamoto M, Nakahara H, Hayashi R, Okimoto T, Monzen Y . Regular surveillance by imaging for early detection and better prognosis of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol. 2009; 45(1):105-12. DOI: 10.1007/s00535-009-0131-x. View

Fontaine H, Lazarus A, Pol S, Pecriaux C, Bagate F, Sultanik P . Bradyarrhythmias Associated with Sofosbuvir Treatment. N Engl J Med. 2015; 373(19):1886-8. DOI: 10.1056/NEJMc1505967. View

Bourliere M, Bronowicki J, de Ledinghen V, Hezode C, Zoulim F, Mathurin P . Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis. 2015; 15(4):397-404. DOI: 10.1016/S1473-3099(15)70050-2. View

Renet S, Chaumais M, Antonini T, Zhao A, Thomas L, Savoure A . Extreme bradycardia after first doses of sofosbuvir and daclatasvir in patients receiving amiodarone: 2 cases including a rechallenge. Gastroenterology. 2015; 149(6):1378-1380.e1. DOI: 10.1053/j.gastro.2015.07.051. View

10.

Lagrutta A, Regan C, Zeng H, Imredy J, Koeplinger K, Morissette P . Cardiac drug-drug interaction between HCV-NS5B pronucleotide inhibitors and amiodarone is determined by their specific diastereochemistry. Sci Rep. 2017; 7:44820. PMC: 5361079. DOI: 10.1038/srep44820. View

11.

Omata M, Kanda T, Wei L, Yu M, Chuang W, Ibrahim A . APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int. 2016; 10(5):702-26. PMC: 5003907. DOI: 10.1007/s12072-016-9717-6. View

12.

Mizokami M, Yokosuka O, Takehara T, Sakamoto N, Korenaga M, Mochizuki H . Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. Lancet Infect Dis. 2015; 15(6):645-53. DOI: 10.1016/S1473-3099(15)70099-X. View

13.

Lawitz E, Poordad F, Pang P, Hyland R, Ding X, Mo H . Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2013; 383(9916):515-23. DOI: 10.1016/S0140-6736(13)62121-2. View

14.

Suzuki Y, Ikeda K, Suzuki F, Toyota J, Karino Y, Chayama K . Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2012; 58(4):655-62. DOI: 10.1016/j.jhep.2012.09.037. View

15.

Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M . Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014; 370(20):1889-98. DOI: 10.1056/NEJMoa1402454. View

16.

. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2013; 60(2):392-420. DOI: 10.1016/j.jhep.2013.11.003. View

17.

Mizokami M, Dvory-Sobol H, Izumi N, Nishiguchi S, Doehle B, Svarovskaia E . Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies. J Viral Hepat. 2016; 23(10):780-8. DOI: 10.1111/jvh.12549. View

18.

Akuta N, Sezaki H, Suzuki F, Fujiyama S, Kawamura Y, Hosaka T . Ledipasvir plus sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens. J Med Virol. 2017; 89(7):1248-1254. DOI: 10.1002/jmv.24767. View

19.

. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015; 62(3):932-54. DOI: 10.1002/hep.27950. View

20.

Miyamura T, Kanda T, Nakamoto S, Wu S, Jiang X, Arai M . Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin. Viruses. 2012; 4(8):1264-78. PMC: 3446761. DOI: 10.3390/v4081264. View