Skip to main content
Erschienen in: Journal of Gastroenterology 3/2019

17.10.2018 | Original Article—Liver, Pancreas, and Biliary Tract

Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures

verfasst von: Mitsutaka Osawa, Michio Imamura, Yuji Teraoka, Takuro Uchida, Kei Morio, Hatsue Fujino, Takashi Nakahara, Atsushi Ono, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Akira Hiramatsu, Hiroshi Aikata, C. Nelson Hayes, Kazuaki Chayama, Hiroshima Liver Study Group

Erschienen in: Journal of Gastroenterology | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Combination therapy with glecaprevir (GLE) and pibrentasvir (PIB) has high efficacy for pan-genotypic hepatitis C virus (HCV)-infected patients. However, the efficacy of the therapy for failures to prior direct-acting antiviral (DAA) regimens in real-world practice is not well known.

Methods

Thirty patients infected with HCV genotype 1b, 2a, 2b, or 3a who failed to respond during prior DAA therapies were treated with GLE/PIB for 12 weeks. HCV NS3 and NS5A drug resistance-associated variants (RAVs) were determined by direct sequencing.

Results

Twenty-eight out of 30 patients (93.3%) achieved SVR12 by GLE/PIB treatment. SVR12 rates were similar between patients with and without advanced liver fibrosis (94.7% and 91.0%, respectively). All 9 patients with genotype 2a, 2b, or 3a HCV infection achieved SVR12. However, two genotype 1b HCV-infected patients who failed previous daclatasvir plus asunaprevir treatment experienced HCV relapse after the end of GLE/PIB treatment. Direct sequence analysis showed the presence of NS3-D168E plus NS5A-L31I/P58S/Y93H RAVs in one patient and NS5A-L31F/P32del RAVs in another patient before GLE/PIB treatment. In the former patient, NS3-D168E plus NS5A-L31I/P58S/Y93H RAVs persisted, and additional NS5A-L28M/V75A variants emerged after HCV relapse.

Conclusions

GLE/PIB treatment for HCV-infected patients who did not respond to prior DAA treatments was highly effective regardless of liver fibrosis stage. However, some genotype 1b HCV-infected patients, especially those with NS5A-P32del, may have low susceptibility to the treatment.
Literatur
2.
Zurück zum Zitat Akuta N, Sezaki H, Suzuki F, et al. Ledipasvir plus sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens. J Med Virol. 2017;89:1248–54.CrossRefPubMed Akuta N, Sezaki H, Suzuki F, et al. Ledipasvir plus sofosbuvir as salvage therapy for HCV genotype 1 failures to prior NS5A inhibitors regimens. J Med Virol. 2017;89:1248–54.CrossRefPubMed
3.
Zurück zum Zitat Teraoka Y, Uchida T, Imamura M, et al. Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure. J Gen Virol. 2018;99:1058–65.CrossRefPubMed Teraoka Y, Uchida T, Imamura M, et al. Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure. J Gen Virol. 2018;99:1058–65.CrossRefPubMed
4.
Zurück zum Zitat Ng T, Tripathi R, Dekhtyar T, et al. In vitro antiviral activity and resistance profile of the next-generation HCV NS3-4A protease inhibitor glecaprevir. Antimicrob Agents Chemother. 2017;62:e01620.CrossRefPubMedPubMedCentral Ng T, Tripathi R, Dekhtyar T, et al. In vitro antiviral activity and resistance profile of the next-generation HCV NS3-4A protease inhibitor glecaprevir. Antimicrob Agents Chemother. 2017;62:e01620.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Ng TI, Krishnan P, Pilot-Matias T, et al. In vitro antiviral activity and resistance profile of the next-generation hepatitis C virus NS5A inhibitor pibrentasvir. Antimicrob Agents Chemother. 2017;61:e02558.CrossRefPubMedPubMedCentral Ng TI, Krishnan P, Pilot-Matias T, et al. In vitro antiviral activity and resistance profile of the next-generation hepatitis C virus NS5A inhibitor pibrentasvir. Antimicrob Agents Chemother. 2017;61:e02558.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis. J Hepatol. 2017;67:263–71.CrossRefPubMed Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis. J Hepatol. 2017;67:263–71.CrossRefPubMed
7.
Zurück zum Zitat Asselah T, Kowdley KV, Zadeikis N, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 Weeks in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2017;16:417–26.CrossRefPubMed Asselah T, Kowdley KV, Zadeikis N, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 Weeks in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2017;16:417–26.CrossRefPubMed
8.
Zurück zum Zitat Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17:1062–8.CrossRefPubMed Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17:1062–8.CrossRefPubMed
9.
Zurück zum Zitat Gane E, Lawitz E, Pugatch D, et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med. 2017;377:1448–55.CrossRefPubMed Gane E, Lawitz E, Pugatch D, et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med. 2017;377:1448–55.CrossRefPubMed
10.
Zurück zum Zitat Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 2017;66:389–97.CrossRefPubMedPubMedCentral Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 2017;66:389–97.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Yoshimi S, Imamura M, Murakami E, et al. Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed daclatasvir and asunaprevir therapy. J Med Virol. 2015;87:1913–20.CrossRefPubMed Yoshimi S, Imamura M, Murakami E, et al. Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed daclatasvir and asunaprevir therapy. J Med Virol. 2015;87:1913–20.CrossRefPubMed
12.
Zurück zum Zitat Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25.CrossRefPubMed Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25.CrossRefPubMed
13.
Zurück zum Zitat Akuta N, Sezaki H, Suzuki F, et al. Retreatment efficacy and predictors of ledipasvir plus sofosbuvir to HCV genotype 1 in Japan. J Med Virol. 2017;89:284–90.CrossRefPubMed Akuta N, Sezaki H, Suzuki F, et al. Retreatment efficacy and predictors of ledipasvir plus sofosbuvir to HCV genotype 1 in Japan. J Med Virol. 2017;89:284–90.CrossRefPubMed
14.
Zurück zum Zitat Backus LI, Belperio PS, Shahoumian TA, et al. Real-world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment-naive, genotype 1 hepatitis C-infected patients. Hepatology. 2016;64:405–14.CrossRefPubMed Backus LI, Belperio PS, Shahoumian TA, et al. Real-world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment-naive, genotype 1 hepatitis C-infected patients. Hepatology. 2016;64:405–14.CrossRefPubMed
15.
Zurück zum Zitat Krishnan P, Schnell G, Tripathi R, et al. Integrated resistance analysis of CERTAIN-1 and CERTAIN-2 studies in HCV infected patients receiving glecaprevir and pibrentasvir in Japan. Antimicrob Agents Chemother. 2017;62:e02217–e02217.CrossRef Krishnan P, Schnell G, Tripathi R, et al. Integrated resistance analysis of CERTAIN-1 and CERTAIN-2 studies in HCV infected patients receiving glecaprevir and pibrentasvir in Japan. Antimicrob Agents Chemother. 2017;62:e02217–e02217.CrossRef
16.
Zurück zum Zitat Itakura M, Kurosaki C, Hasebe Y, et al. Complex pattern of resistance-associated substitutions of hepatitis C virus after daclatasvir/asunaprevir treatment failure. PLoS One. 2016;11:e0165339.CrossRefPubMedPubMedCentral Itakura M, Kurosaki C, Hasebe Y, et al. Complex pattern of resistance-associated substitutions of hepatitis C virus after daclatasvir/asunaprevir treatment failure. PLoS One. 2016;11:e0165339.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Gottwein JM, Pham LV, Mikkelsen LS, et al. Efficacy of NS5A inhibitors against hepatitis C virus genotypes 1–7 and escape variants. Gastroenterology. 2018;154:1435–48.CrossRefPubMed Gottwein JM, Pham LV, Mikkelsen LS, et al. Efficacy of NS5A inhibitors against hepatitis C virus genotypes 1–7 and escape variants. Gastroenterology. 2018;154:1435–48.CrossRefPubMed
18.
Zurück zum Zitat Kumada H, Watanabe T, Suzuki F, et al. Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection. J Gastroenterol. 2017;53:566–75.CrossRefPubMedPubMedCentral Kumada H, Watanabe T, Suzuki F, et al. Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection. J Gastroenterol. 2017;53:566–75.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Teraoka Y, Uchida T, Imamura M, et al. Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice. Biochem Biophys Res Commun. 2018;500:152–7.CrossRefPubMed Teraoka Y, Uchida T, Imamura M, et al. Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice. Biochem Biophys Res Commun. 2018;500:152–7.CrossRefPubMed
20.
Zurück zum Zitat Gane EJ, Shiffman ML, Etzkorn K, et al. Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct-acting antiviral regimen. Hepatology. 2017;66:1083–9.CrossRefPubMed Gane EJ, Shiffman ML, Etzkorn K, et al. Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct-acting antiviral regimen. Hepatology. 2017;66:1083–9.CrossRefPubMed
21.
Zurück zum Zitat Lawitz E, Poordad F, Wells J, et al. Sofosbuvir-velpatasvir-voxilaprevir with or without ribavirin in direct-acting antiviral—experienced patients with genotype 1 hepatitis C virus. Hepatology. 2017;65:1803–9.CrossRefPubMed Lawitz E, Poordad F, Wells J, et al. Sofosbuvir-velpatasvir-voxilaprevir with or without ribavirin in direct-acting antiviral—experienced patients with genotype 1 hepatitis C virus. Hepatology. 2017;65:1803–9.CrossRefPubMed
Metadaten
Titel
Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures
verfasst von
Mitsutaka Osawa
Michio Imamura
Yuji Teraoka
Takuro Uchida
Kei Morio
Hatsue Fujino
Takashi Nakahara
Atsushi Ono
Eisuke Murakami
Tomokazu Kawaoka
Daiki Miki
Masataka Tsuge
Akira Hiramatsu
Hiroshi Aikata
C. Nelson Hayes
Kazuaki Chayama
Hiroshima Liver Study Group
Publikationsdatum
17.10.2018
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 3/2019
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-018-1520-9

Weitere Artikel der Ausgabe 3/2019

Journal of Gastroenterology 3/2019 Zur Ausgabe

Acknowledgment

Acknowledgements

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.